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The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD., Objectives: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD., Methods: We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention., Results: About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFβ, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFβ and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis., Conclusions: Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Aim: To evaluate the protein profiles in gingival crevicular fluid (GCF) in relation to clinical outcomes after periodontal surgery and examine if any selected proteins affect the mRNA expression of pro-inflammatory cytokines in human gingival fibroblasts., Materials and Methods: This exploratory study included 21 consecutive patients with periodontitis. GCF was collected, and the protein pattern (n = 92) and clinical parameters were evaluated prior to surgery and 3, 6 and 12 months after surgery. Fibroblastic gene expression was analysed by real-time quantitative polymerase chain reaction., Results: Surgical treatment reduced periodontal pocket depth (PPD) and changed the GCF protein pattern. Twelve months after surgery, 17% of the pockets showed an increase in PPD. Levels of a number of proteins in the GCF decreased after surgical treatment but increased with early signs of tissue destruction, with LIGHT being one of the proteins that showed the strongest association. Furthermore, LIGHT up-regulated the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6, IL-8 and MMP9 in human gingival fibroblasts., Conclusions: LIGHT can potentially detect subjects at high risk of periodontitis recurrence after surgical treatment. Moreover, LIGHT induces the expression of inflammatory cytokines and tissue-degrading enzymes in gingival fibroblasts., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background and Objective: Protease-activated receptor-2 (PAR 2 ), a pro-inflammatory G-protein coupled receptor, has been associated with pathogenesis of periodontitis and the resulting bone loss caused by oral pathogens, including the keystone pathogen Porphyromonas gingivalis (P. gingivalis). We hypothesised that administration of a PAR 2 antagonist, GB88, might prevent inflammation and subsequent alveolar bone resorption in a mouse model of periodontal disease., Methods: Periodontitis was induced in mice by oral inoculations with P. gingivalis for a total of eight times over 24 days. The infected mice were treated with either GB88 or vehicle for the duration of the trial. Following euthanasia on day 56, serum was collected and used for the detection of mast cell tryptase. The right maxillae were defleshed and stained with methylene blue to measure the exposed cementum in molar teeth. The left maxillae were prepared for cryosections followed by staining for tartrate-resistant acid phosphatase to identify osteoclasts or with toluidine blue to identify mast cells. Reverse transcription quantitative PCR (RT-qPCR) was used to quantify the expression of inflammatory cytokines in the gingival tissue. Supernatants of T-lymphocyte cultures isolated from the regional lymph nodes were assayed using a cytometric bead array to measure the Th1/Th2/Th17 cytokine levels., Results: Measurement of the exposed cementum showed that GB88 reduced P. gingivalis-induced alveolar bone loss by up to 69%. GB88 also prevented the increase in osteoclast numbers observed in the infected mice. Serum tryptase levels were significantly elevated in both the infected groups, and not altered by treatment. RT-qPCR showed that GB88 prevented the upregulation of Il1b, Il6, Ifng and Cd11b. In T-lymphocyte supernatants, only IFNγ and IL-17A levels were increased in response to infection, but this was prevented by GB88 treatment., Conclusions: GB88 significantly reduced osteoclastic alveolar bone loss in mice infected with P. gingivalis, seemingly by preventing the upregulation of several inflammatory cytokines. PAR 2 antagonism may be an effective treatment strategy for periodontal disease., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Background: The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO-high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood., Objectives: To explore airway pathology in T2 biomarker-high and -low severe asthma., Methods: T2 biomarker-high severe asthma (T2-high, n = 17) was compared with biomarker-intermediate (T2-intermediate, n = 21) and biomarker-low (T2-low, n = 20) severe asthma and healthy controls (n = 28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD 2 and LTE 4 measurements., Results: Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodelling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared with health, but similar across asthma subgroups. Submucosal glands were increased in T2-intermediate and T2-low asthma. In spite of similar tissue cellular inflammation, sputum IL-4, IL-5 and CCL26 were increased in T2-high versus T2-low asthma, and several further T2-associated cytokines, PGD 2 and LTE 4 , were increased in T2-high and T2-intermediate asthma compared with healthy controls., Conclusions: Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker-high and T2-low severe asthma, but inflammatory and structural cell activation is present, with sputum T2-associated cytokines highest in T2 biomarker-high patients. Airway remodelling persists and may be important for residual disease expression beyond eosinophilic exacerbations. Registered at ClincialTrials.gov: NCT02883530., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: To compare pro-inflammatory cytokine levels in the peri-implant crevicular fluid (PICF) in unused and reused healing abutments., Materials and Methods: This study was a controlled randomized, double-blind clinical trial. Seventy-two patients who met the inclusion criteria were divided into two groups. After one-stage implant placement, in group A, an unused healing abutment, and in group B, a reused healing abutment, was connected to the implant fixture. After 2 months, clinical measurements for keratinized gingiva (KG), plaque index (PI), and bleeding index (BI) (Ainamo and Bay) were taken, and PICF sampling was performed to evaluate pro-inflammatory IL-1β and TNF-α cytokine levels using the ELISA test. Comparison of clinical measurements and cytokine levels between the two study groups was made using the Mann-Whitney test., Result: Clinical measurements and sampling were performed on 60 patients (nA = 27, nB = 33). There was no significant difference between the two groups in clinical measurements (BI (p = 0.96) and PI (p = 0.06)) or TNF-α (p = 0.63), and IL-1β (p = 0.26) cytokine levels., Conclusion: Reused healing abutments that are cleaned and sterilized properly do not appear to induce further peri-implant pro-inflammatory response; therefore, they can be utilized temporarily until implant abutment insertion., (© 2021 The Authors. Journal of Prosthodontics published by Wiley Periodicals LLC on behalf of American College of Prosthodontists.)

Aim: To investigate the relationship between cytokine profiles and "fast" and "slow" patterns of gingival inflammation development., Materials and Methods: Forty-two adults participated in an experimental gingivitis study, comprising a 2-week hygiene phase (clinical examination and professional cleaning); a 3-week induction phase (absence of oral hygiene); and a 2-week resolution phase (re-establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumour necrosis factor-alpha (TNF-α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group-based-trajectory-modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed-effects modelling., Results: GBTM analysis revealed two cytokine profiles, "non-organized response" (IL-4, IL-6, IL-8, IL-12, and IL-13) and "organized response" (IL-2, IL-10, and TNF-α). Among the "slow" responders, neither cytokine profile was associated with gingivitis. In contrast, a "fast" response was associated with a higher "non-organized response" factor (coef. 0.14) and a lower "organized response" factor (coef. -0.03)., Conclusion: A "fast" gingivitis development was associated with a higher "non-organized response" and a lower "organized response", which may elucidate the role of individual variability in gingivitis susceptibility., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment., Background: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1β, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1., Materials and Methods: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment., Results: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1β, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed., Conclusion: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Vegetarian diets are known to reduce inflammation. The objective of this study was to test the hypothesis that reduced inflammation associated with a vegetarian diet would promote a more commensal subgingival bacterial profile., Methods: A total of 39 periodontally healthy subjects (PD ≤3 mm, bleeding on probing <10%) were enrolled. Dietary intake was assessed by a food frequency questionnaire. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and subgingival plaque samples were collected. GCF samples were assessed for interleukin-1β, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and interleukin-10. Plaque samples were analyzed for bacteria using 16S rDNA sequencing on an Illumina platform. GenBank database was used for taxonomy classification., Results: Twenty-three subjects were categorized as vegetarian and 16 non-vegetarians. Clinical periodontal measures and GCF cytokine levels were statistically comparable between the two groups. Measures of microbial richness and alpha diversity were also comparable between the two dietary groups. Vegetarians harbored higher levels of phyla associated with gingival health (Actinobacteria, and Proteobacteria). Two species known to be associated with periodontitis (Mogibacterium timidum and Veillonella rogosae) were prominent in non-vegetarians. Pearson's correlations between GCF inflammatory cytokines and microbial taxa differed between vegetarians and non-vegetarians. In vegetarians, the anti-inflammatory cytokine IL-10 positively correlated with two species known to be associated with periodontal health (Peptidiphaga sp. HMT183 and Rothia aeria)., Conclusions: Diet is directly and indirectly associated with the microbial composition of subgingival plaque. A vegetarian diet may promote a subgingival microbiota associated with periodontal health., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Inflammatory cytokines are key regulators of inflammation, but current measurement approaches require venous blood to quantify low circulating concentrations associated with chronic, low-grade inflammation. This article describes a highly sensitive multiplex immunoassay protocol for the measurement of IL6, IL8, IL10, and TNFα in finger stick dried blood spot (DBS) samples., Methods: The protocol uses a multiplex electrochemiluminescent immunoassay platform. The following measures of assay performance were evaluated: reliability (inter-assay percent coefficient of variation; %CV), precision (intra-assay %CV), lower limit of detection (LLD), linearity of dilution, and agreement with results from matched plasma samples., Results: Analysis of three control samples across the assay range indicated an acceptable level of precision and reliability for each cytokine. Linearity of dilution returned average values that ranged from 104.1 to 127.6% of expected. Lower limits of detection for IL6, IL8, and IL10 were <0.5, and <1.0 pg/ml for TNFα. Level of agreement in results between matched DBS and plasma samples was high for all cytokines except for IL8., Conclusions: Finger stick DBS sampling provides a viable alternative to venipuncture for the quantification of IL6, IL10, and TNFα at low concentrations associated with chronic inflammation. The presence of red blood cells may interfere with the quantification of IL8 in DBS. In facilitating blood collection in nonclinical settings this method can advance scientific understandings of how social and ecological contexts shape immune function and health over the life course., (© 2020 Wiley Periodicals LLC.)

Background Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD-mediated cardiac improvement to guide patient selection, treatment, and monitoring. Methods and Results Ninety-three patients requiring durable LVAD were prospectively enrolled. Myocardial tissue and blood were acquired during LVAD implantation, for measurement of inflammatory markers. Cardiac structural and functional improvement was prospectively assessed via serial echocardiography. Eleven percent of the patients showed significant reverse remodeling following LVAD support (ie, responders). Circulating tumor necrosis factor alpha, interleukin (IL)-4, IL-5, IL-6, IL-7, IL-13, and interferon gamma were lower in responders, compared with nonresponders ( P <0.05, all comparisons). The myocardial tissue signal transducer and activator of transcription-3, an inflammatory response regulator, was less activated in responders ( P =0.037). Guided by our tissue studies and a multivariable dichotomous regression analysis, we identified that low levels of circulating interferon gamma (odds ratio [OR], 0.06; 95% CI, 0.01-0.35) and tumor necrosis factor alpha (OR, 0.05; 95% CI, 0.00-0.43), independently predict cardiac improvement, creating a 2-cytokine model effectively predicting responders (area under the curve, 0.903; P <0.0001). Conclusions Baseline myocardial and systemic inflammatory burden inversely correlates with cardiac improvement following LVAD support. A circulating 2-cytokine model predicting significant reverse remodeling was identified, warranting further investigation as a practical preintervention tool in identifying patients prone to LVAD-mediated cardiac improvement and device weaning.

Objective: We studied cytokines in gingival crevicular fluid (GCF) in a cross-sectional population-based cohort of rheumatoid arthritis (RA) patients ≥61 years of age with and without a diagnosis of periodontitis., Background Data: Earlier studies on cytokines in GCF in RA patients have not given clear results., Methods: In a population-based cross-sectional study of patients ≥61 years of age, 233 RA patients were identified. 132 (57%) dentate RA patients participated. All participants received rheumatological and dental examinations, and had a panoramic radiograph taken. GCF was sampled on each patient. Interleukins 1-β (IL-1β), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and chemokines RANTES/CCL5, eotaxin and monocyte chemoattractant protein (MCP-1) were analyzed in GCF. These cytokines were stratified for periodontitis, age, gender, body mass index (BMI), smoking, and anti-cyclic citrullinated protein (anti-CCP) status. Binary logistic regression analyses with periodontitis as outcome were performed adjusting for the above mentioned confounding factors including anti-rheumatic medication, disease duration and the cytokine in question., Results: Periodontitis was diagnosed in 80/132 (61%) of study participants. The 110 RA patients not participating were older, had a higher mean erythrocyte sedimentation rate (ESR), had a higher mean DAS28ESR (Disease Activity Score 28 using ESR) and were less often on biologic treatment. Only RANTES was associated with periodontitis (p = .049, OR 1.001, 95% CI 1.000-1.002) in the binary logistic regression analyses., Conclusion: In this population-based elderly RA cohort, neither pro-inflammatory nor anti-inflammatory cytokines in GCF were clearly associated with a diagnosis of periodontitis., (© 2021 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Aim: To evaluate the local immunoinflammatory profiles in localized aggressive periodontitis patients (LAP) before and after periodontal treatment and maintenance., Methods: Sixty-six African-Americans with LAP (7-21 years old) were included. After periodontal examination, all patients received periodontal treatment with mechanical debridement plus systemic amoxicillin/metronidazole for 7 days. Gingival crevicular fluid was collected from diseased and healthy sites at baseline and 3, 6, 12, and 24 months following treatment. Levels of 16 inflammatory/bone resorption markers were determined using Milliplex ® . Univariate and correlation analyses were performed among all parameters/biomarkers. Discriminant analyses (DA) evaluated profile differences between LAP diseased and healthy sites at each time point as compared to the baseline., Results: Reductions in the clinical parameters (except for visible plaque) were observed at all time points compared to the baseline. Levels of IL-12p70, IL-2, IL-6, MIP-1α, RANKL, and OPG were reduced after treatment, and several cytokines/chemokines were correlated with clinical parameters reductions. DA showed that differences in the immunoinflammatory profiles between LAP diseased and healthy sites decreased after periodontal treatment compared to the baseline., Conclusions: Periodontal treatment modified the local immunoinflammatory profile of LAP sites in the long term, as suggested by changes in biomarkers from baseline, along with clinical stability of the disease. (Clinicaltrials.gov number, NCT01330719)., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX promotor )-controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX promotor -AIM2 adenoviruses (Ad-CAIX promotor -AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad-CAIX promotor , Ad-CAIX promotor -AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786-O cells or OSRC-2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC-2-xenograft mice. The tumour growth was remarkably inhibited in Ad-CAIX promotor -AIM2-treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD-CMK resulted in the reduction of anti-tumour activity by Ad-CAIX promotor -AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad-CAIX promotor -AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour-specific Ad-CAIX promotor -AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2-based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Sodium tanshinone IIA sulfonate (STS) has been reported to prevent Alzheimer's disease (AD). However, the mechanism is still unknown. In this study, two in vitro models, Aβ-treated SH-SY5Y cells and SH-SY5Y human neuroblastoma cells transfected with APPsw (SH-SY5Y-APPsw cells), were employed to investigate the neuroprotective of STS. The results revealed that pretreatment with STS (1, 10 and 100 µmol/L) for 24 hours could protect against Aβ (10 µmol/L)-induced cell toxicity in a dose-dependent manner in the SH-SY5Y cells. Sodium tanshinone IIA sulfonate decreased the concentrations of reactive oxygen species, malondialdehyde, NO and iNOS, while increased the activities of superoxide dismutase and glutathione peroxidase in the SH-SY5Y cells. Sodium tanshinone IIA sulfonate decreased the levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in the SH-SY5Y cells. In addition, Western blot results revealed that the expressions of neprilysin and insulin-degrading enzyme were up-regulated in the SH-SY5Y cells after STS treatment. Furthermore, ELISA and Western blot results showed that STS could decrease the levels of Aβ. ELISA and qPCR results indicated that STS could increase α-secretase (ADAM10) activity and decrease β-secretase (BACE1) activity. In conclusion, STS could protect against Aβ-induced cell damage by modulating Aβ degration and generation. Sodium tanshinone IIA sulfonate could be a promising candidate for AD treatment., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objective: To evaluate the role of natural curcumin (CURC) on experimental periodontitis (EP) in animals with diabetes mellitus (DM)., Material and Methods: One hundred rats were assigned to DM + placebo (PLA); DM + CURC; DM + insulin (INS); DM + CURC + INS; and Non-DM. Diabetes was induced by streptozotocin. After 3 days, they were initiated CURC and PLAC solutions and insulin administrations, daily for 30 days. This included a period of 19 days prior to EP induction (ligature at the first mandibular and the second maxillary molar) and then additional 11 days. Specimens from the mandible were processed for morphometric examination of bone level. Gingival tissues from mandibular molars were collected for quantification of IL-1β, IL-4, IL-6, IL-17, IFN-γ, and TNF-α using a Luminex/MAGpix assay. Gingivae from maxillary molars were subjected to RT-PCR for assessment of Runx2, RANKL, OPG, SIRT, Dkk1, and Sost levels., Results: Lower linear bone loss was detected in ligated molars of DM + CURC + INS vs DM + PLAC and DM + INS groups (P < 0.05). In ligated sites from DM rats treated with CURC + INS, IL-6, IL-1β, INF-γ, and TNF-α levels were the lowest in comparison with PLAC and/or INS and CURC as monotherapies (P < 0.05). CURC, independently of INS, increased Runx2 and SIRT when compared to DM + PLAC (P < 0.05) in ligated sites, whereas only CURC + INS reduced the RANKL/OPG ratio when compared to DM + PLAC (P < 0.05)., Conclusion: Natural CURC, when associated with INS, reduces the DM-induced loss of supporting alveolar bone and promotes favorable modulation on osteo-immune-inflammatory mediators., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic persistent stress is an important cause of gastritis, but the underlying mechanism remains to be further researched, especially the role of the gastric microbiota in this process. Here, we used the water avoidance stress (WAS) test in mouse models for chronic stress-induced gastritis to investigate the underlying mechanisms of this disease. The effect of stress on the gastric microbiota was analyzed based on 16S rRNA sequencing; the changes in hydrogen sulfide (H 2 S) and inflammatory cytokine levels in gastric tissues were detected by Western blotting, ELISA, immunofluorescence, and qRT-PCR. Hematoxylin and eosin staining was used as an indicator of the gastritis histological score. This finding is consistent with previous studies showing that gastric H 2 S is negatively associated with the inflammatory index and might protect the gastrointestinal tract from inflammation. WAS-induced gastritis was associated with a reduction in H 2 S release, which appeared to affect the homeostasis of the gastric microbiota of mice. Inflammation and microbial dysbiosis were partially reversed by sodium hydrosulfide (NaHS) and vitamin B6 (VB6) supplementation, suggesting the therapeutic potential of VB6 supplementation for the treatment of stress-induced gastritis. Gastritis has a serious impact on health and quality of life. An increasing number of people are suffering from chronic gastritis linked to a high-stress lifestyle, and our research provides clues for the prevention and treatment of stress-induced gastritis., (© 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Objective: The purpose of this study was to investigate involvement of the P2X7 receptor in the rare condition, localized aggressive periodontitis., Material and Methods: Peripheral blood from 220 African Americans (103 with localized aggressive periodontitis and 117 healthy unrelated controls) was stimulated with lipopolysaccharide from E coli and Porphyromonas gingivalis. P2RX7 single nucleotide polymorphisms rs208294 (H155Y), rs1718119 (T348A), rs2230911 (T357S) and rs3751143 (E496A) were genotyped in 103 localized aggressive periodontitis patients and 117 healthy unrelated subjects. We examined genetic association between four P2RX7 single nucleotide polymorphisms and localized aggressive periodontitis, and tested for correlations between the single nucleotide polymorphisms and inflammatory response to lipopolysaccharide in blood samples from these patients., Results: A significant association with localized aggressive periodontitis was observed with rs1718119 A (Thr) allele (P = 0.0063, odds ratio = 1.904) and with a haplotype containing this allele (P = 0.0075). Additionally, significant correlations with these data were found: the rs1718119 G allele correlated with greater production of IL-6, IL-2 and GM-CSF; the C (His) allele of rs208294 correlated with lower levels of IL-12p40; and the C (Thr) allele of rs2230911 correlated with greater levels of G-CSF., Conclusion: The data from these analyses support a possible biological relationship between P2RX7 genetic variants and inflammatory response in localized aggressive periodontitis patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro-inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells-1 (TREM-1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM-1 expression. However, whether TREM-1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM-1 knock-out (Trem-1 -/- ) mice were used to inhibit TREM-1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM-1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM-1 on endometritis during LPS infection and indicate that blocking of TREM-1 in LPS-induced endometritis holds considerable promise for blunting excessive inflammation., (© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

We sought to explore the functions and modulated factors of NOD1 in normal decidual stromal cells (DSCs) derived from the first trimester pregnancy and whether existed different expression of NOD1 between normal and unexplained recurrent pregnancy loss (URPL) in DSCs. Twenty-six patients with normal pregnancies that required abortion and 12 URPL patients at first trimester were enrolled for the study. As a result, we found lower levels of NOD1 in the DSCs derived from URPL compared with those from normal early trimester pregnancy. Furthermore, increased NOD1 expression in the normal DSCs induced apoptosis and increased monocyte chemotactic protein-1 (MCP-1) and IL-1β (interleukin 1 beta) secretion but decreased their invasion capacity. In addition, several cytokines such as IL-1β, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-17 (IL-17) were present at the maternal-fetal interface in RPL and were found to regulate NOD1 expression in primary DSCs. Our study indicates that RPL may be associated with NOD1 aberrant expression in DSCs, which plays a significant role in maintaining pregnancy via infection control and regulation of immune responses that might affect the pregnancy outcome. We expect that our results will bring more comprehensively understanding about the connection between NOD1 and RPL for researchers., (© 2019 John Wiley & Sons, Ltd.)

Aim: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury., Methods: EHD2-sc-mTNF R2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation., Results: The activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNF R2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation., Conclusion: The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation., (© 2019 CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial (NCT01920893)., Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks., Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin-3 (-30.06 vs -0.86 pg/mL; P = 0.0008) and total IgE (-7.90 vs -1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin-2 (P = 0.008), eotaxin-3 (P = 0.031), pulmonary and activation-regulated chemokine (P = 0.016), IgE (P = 0.023), and IL-13 (P = 0.031)., Conclusions: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Objectives: Previous research has established population variation in anti-inflammatory immunological biomarkers in human milk. This immunity is potentially ecology-dependent and may alter the life history trade-off between growth and maintenance in infants. The current study has two aims: (1) to assess the ecological differences in milk immunity in two populations, one from the urban U.S. and one from rural Kenya; and (2) to test the hypothesis that milk immunity can affect infant growth indicators., Materials and Methods: Kenyan Ariaal (n = 233) and U.S. (n = 75) breastfeeding mother-infant pairs participated in a cross-sectional study at two separate field sites. Laboratory analysis was performed on milk for the anti-inflammatory biomarkers TGF-β2, sTNF-αRI, sTNF-αRII, and IL-1ra using ELISA. Multiple imputation was used to extrapolate data below the limit of detection before multivariate analysis., Results: There were significant differences between U.S. and Kenyan mothers on all four milk biomarkers, with Kenyan mothers having significantly higher sTNF-αRI and sTNF-αRII and lower TGF-β2 and IL-1ra than U.S. mothers. U.S. mothers with higher milk TGF-β2 and IL-1ra have infants that are significantly longer and heavier for their age, while Kenyan mothers with higher sTNF-αRI have significantly longer and heavier infants for their age, and those with higher TGF-β2 have marginally significantly longer infants., Discussion: There were significant differences in ecological milk immunity between U.S. and Kenyan mothers. These differences potentially play a role in the growth of their infants. Further research in milk immunity should consider the possibility of shared maternal-infant life histories., (© 2018 Wiley Periodicals, Inc.)

Short-chain fatty acids (SCFAs), particularly butyrate, are known to suppress inflammation, and regulate the gut bacterial ecology. However, little is known about propionate. We report here that propionate infusion in the caecum dramatically affected the structure of colonic microbiota of pigs based on 16s rRNA high-throughput sequencing. Sixteen pig models were perfused with saline or sodium propionate by a fistula in the caecum. At d 28, all pigs were slaughtered for analysing bacterial metabolites, colonic microbiota and the expression of genes related to inflammation. The results showed that caecal infusion of sodium propionate increased the concentration of propionate and decreased the butyrate concentration in colonic content. For biogenic amines, the tyramine concentration was increased, while the concentration of cadaverine was decreased by infusion of sodium propionate. Furthermore, at the level of phylum, propionate increased the abundance of Bacteroidetes and reduced the abundance of Firmicutes. Prevotella and Bacteroides counts were increased, while Turicibacter abundance was decreased at the level of genus. Real-time qPCR showed that the expression of NF-κB and IL-18 was upregulated by propionate infusion, whereas no significant differences were observed for the expression of other genes related to inflammatory processes. Taken together, these results provide a new evidence for the role of short-chain fatty acid propionate on the composition of microbial community and inflammatory cytokines., (© 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

In the present study, the impact of scaling and root planing (SRP) on gingival crevicular fluid (GCF) cytokine/chemokine levels in smokers with chronic periodontitis was assessed. The PICO (population, intervention, comparison, outcome) question was: In smokers with chronic periodontitis (population), what is the effect of SRP (intervention) in comparison to SRP in non-smokers with chronic periodontitis (comparison) on the GCF cytokine/chemokine level (outcome)? Indexed databases were searched up to September 2017. Of 4330 titles, nine studies reporting the levels of 13 different cytokines/chemokines were included. Eight studies had a moderate risk of bias, while one study had a high risk of bias. Almost all cytokines/chemokines were pro-inflammatory cytokines. Five cytokines/chemokines studied in four clinical studies were decreased in the smoker-chronic periodontitis group following SRP. One study observed that the GCF levels of interleukin-17 increased, while anti-inflammatory osteoprotegerin was reduced in both the SCP and non-smoker-chronic periodontitis groups at follow up. However, the majority of cytokines/chemokines did not change in the SCP groups at follow up. The current weight of evidence is not sufficient to prove that SRP has an impact on GCF cytokine/chemokine profile in smokers with chronic periodontitis. Evaluation of wide panels of pro-inflammatory cytokines/chemokines related to collagen degradation and alveolar bone destruction in future studies are warranted., (© 2018 John Wiley & Sons Australia, Ltd.)

Background and Objective: Glycine powder air-polishing (GPAP) is an alternative approach to removing subgingival plaque biofilms for effective periodontal therapy. This study aimed to investigate the effect of subgingival GPAP as an additional approach to nonsurgical periodontal treatment in subjects with chronic periodontitis., Material and Methods: Twenty-seven nonsmoking subjects were recruited. Two quadrants in each subject were randomly assigned, according to a split-mouth design, to receive scaling and root planing (SRP) and GPAP (Test group) or SRP and air flushing with water (Control group) at sites with probing depth ≥5 mm. Clinical parameters, gingival crevicular fluid volumes and the concentrations of interleukin-1β and interleukin-1ra in gingival crevicular fluid were measured at baseline and 1, 3 and 6 months after the treatments., Results: At baseline, no statistically significant difference in periodontal and gingival crevicular fluid parameters was found between the Test and Control groups. Overall, the periodontal conditions of all subjects showed significant improvement after the treatments. Notably, the Test group showed greater reduction in gingival crevicular fluid volume (0.37 ± 0.26 μL) than the Control group (0.23 ± 0.30 μL) at 3 months (P < .05). The gingival crevicular fluid levels of interleukin-1β and interleukin-1ra showed a significant decrease in both groups at 6 months, and no significant difference was found between the groups., Conclusion: These preliminary results suggest that GPAP, as an additional approach to nonsurgical periodontal treatment, may be beneficial for the short-term improvement of subclinical inflammation when measured by gingival crevicular fluid volume. Further longitudinal studies with larger sample sizes are required to clarify the exact benefits of GPAP treatment for controlling inflammation and maintaining long-term periodontal health., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine whether the concentration and distribution of immune markers in paired oral samples were similar., Study Type: Clinical research., Study Design: Cross-sectional study., Methods: Paired saliva and oral secretions (OS) samples were collected. The concentration of immune markers was estimated using Luminex multiplex assay (Thermo Fisher Scientific, Waltham, MA). For each sample, the concentration of respective immune markers was normalized to total protein present and log-transformed. Median concentrations of immune markers were compared between both types of samples. Intermarker correlation in each sampling method and across sampling methods was evaluated., Results: There were 90 study participants. Concentrations of immune markers in saliva samples were significantly different from concentrations in OS samples. Oral secretions samples showed higher concentrations of immunoregulatory markers, whereas the saliva samples contained proinflammatory markers in higher concentration., Conclusion: The immune marker profile in saliva samples is distinct from the immune marker profile in paired OS samples., Level of Evidence: 2b. Laryngoscope, 128:E214-E221, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: To evaluate the effects of physical training on inflammatory and behavioural parameters of Wistar rats with periodontal disease (PD)., Materials and Methods: Twenty four animals were distributed in a 2 × 2 factorial design (with and without exercise, with and without PD). Trained animals swimmed one hour daily during 8 weeks. PD was induced by ligature 14 days before the end of experiment, and in the last week, all animals were submitted to the Marble Burying Test. Histomorphometric analyses of the mandibles and expression of cytokines were conducted by Western blotting. We also evaluated the morphometry of hippocampal astrocytes using anti-glial fibrillary acidic protein antibody., Results: Physical training attenuated bone loss and epithelial attachment loss levels of rats with PD. Trained animals with PD presented lower TNF-α expression in periodontal tissues while IL-10 was increased. TNF-α/IL-10 ratio was lower in trained animals with PD compared to those with induced periodontitis. PD increased anxiety-like behaviour, and physical training attenuated this parameter. Exercise increased the ramifications of hippocampal astrocytes in rats without PD., Conclusions: Exercise decreased anxiety behaviour, inflammatory proteins expression and bone loss in rats with PD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Two new T-helper (Th) phenotypes have been recently described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study was aimed to assess whether Th9 and Th22 lymphocytes, through interleukin (IL)-9 and IL-22 production, respectively, are associated with the severity of periodontitis and bone resorption., Material and Methods: Gingival crevicular fluid samples and biopsies were obtained from patients with moderate-to-advanced chronic periodontitis and gingivitis, and healthy controls. The levels for the Th9 and Th22-associated cytokines and master-switch transcription factors Spi-B and aryl hydrocarbon receptor (AhR) were quantified by enzyme-linked immunosorbent assay, real-time reverse-transcription quantitative polymerase chain reaction and flow cytometry. In addition, the osteoclast activity in response to tissue homogenates from periodontitis and healthy samples was analyzed quantifying the number of TRAP-positive cells and areas of bone resorption pits produced, in the presence or absence of recombinant human IL-22 and anti-IL-22 neutralization antibody., Results: Higher levels of IL-22 and AhR were detected in patients with periodontitis compared with gingivitis and healthy individuals. In addition, higher levels of IL-9 and Spi-B were detected in gingivitis patients compared with periodontitis and healthy individuals. In patients with periodontitis, a significant positive correlation was detected between secreted levels of IL-22 and clinical attachment level of the sampled periodontal pockets. When osteoclasts were exposed to tissue homogenates obtained from patients with periodontitis, higher levels of resorptive activity were observed as compared with the same cells exposed to tissue homogenates obtained from healthy individuals, and this increment was dependent on the presence and neutralization of IL-22., Conclusion: Increased levels of IL-22 produced by Th22 lymphocytes are associated with the pathogenesis of periodontitis, in particular, with osteoclast resorptive activity and severity of disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Periodontal disease is a chronic inflammatory disease caused by bacterial infection that can lead to tooth loss. Gingival crevicular fluid can be collected easily and noninvasively. We previously discovered the presence of apolipoprotein B (apoB), the main constituent of low-density lipoprotein, and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid of healthy subjects. In this study, we investigated whether periodontal conditions affect the levels of apoB and oxLDL in gingival crevicular fluid., Material and Methods: The study population comprised 11 patients with chronic periodontitis. A pair of gingival crevicular fluid samples was collected from each patient at a healthy site and at a site with periodontitis (baseline samples). Thereafter, gingival crevicular fluid samples were collected from the same patients again at 4 and 8 wk after scaling and root planing (SRP). The levels of apoB, oxLDL, protein and cytokines in gingival crevicular fluid, in addition to gingival crevicular fluid volume, were measured., Results: At baseline, the levels of apoB and oxLDL in gingival crevicular fluid were higher at the sites with periodontitis than at the healthy sites. The levels of apoB and oxLDL at periodontal sites decreased after SRP. The level of oxLDL in gingival crevicular fluid correlated well with the probing pocket depth. The oxLDL : apoB ratio in gingival crevicular fluid was significantly higher than that in plasma., Conclusions: The levels of apoB and oxLDL in gingival crevicular fluid change according to the periodontal tissue conditions., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Helicobacter pylori can cause many gastrointestinal and also extra-gastrointestinal disorders and is a major risk factor for gastric carcinoma and MALT lymphoma. Currently, numerous antibiotic-based therapies are available; however, these therapies have numerous drawbacks, mainly due to increasing prevalence of antibiotic resistant strains. Thus, there is an urgent need to develop novel therapeutic agents against H. pylori infections., Materials and Methods: In this study, the anti-H. pylori activity of 2:1 mixture of Satureja hortensis and Origanum vulgare subsp. hirtum essential oils (2MIX) was investigated in vivo. After screening in vitro cytotoxicity of 2MIX on mammalian cell lines, the therapeutic efficiency was studied in a mouse model, where changes in H. pylori colonization were detected by PCR and histology of gastric samples. The immune reaction of mice was tested based on cytokine and chemokine production, and the in vivo toxicity of 2MIX was also investigated by measuring ALT and AST enzyme activities and Cyp3a11 and HO-1 mRNA levels in livers of mice., Results: 2MIX had not shown in vitro cytotoxicity against cell lines, only the highest concentration caused significant decrease in their survival rates. In the in vivo experiments, 2MIX successfully eradicated the pathogen in 70% of the mice. We could not detect toxicity or altered cytokine and chemokine balance after in vivo treatments in mice., Conclusions: These results show that 2MIX is effective in reducing H. pylori colonization suggesting that this essential oil mixture has great potential as a new, effective, and safe therapeutic agent against H. pylori., (© 2016 John Wiley & Sons Ltd.)

Background: Knowledge of sepsis-related end-organ inflammation in vivo is limited. We investigated the cytokine response in skin and in serum in sepsis and its relation to multiorgan failure (MOF) and survival., Methods: Cytokines were analysed in serum and in suction blister fluid of intact skin of 44 patients with severe sepsis and 15 healthy controls. Blister fluid and serum samples were collected within 48 h of the first sepsis-induced organ failure. This is a substudy of a larger follow-up study on wound healing in sepsis., Results: Cytokine levels were higher in patients with sepsis vs. controls (interleukin [IL]-10, blisters: 65.9 vs. 4.3 pg/ml, P < 0.001, serum: 25.7 vs. 4.5 pg/ml, P = 0.004; IL-6, blisters: 41.9 vs. 0.03 pg/ml, P < 0.001, serum: 45.5 vs. 2.1 pg/ml, P < 0.001). Patients with MOF had higher levels of IL-10 (116.4 vs. 21.3 pg/ml, P = 0.015), IL-4 (0.7 vs. 0.07 pg/ml, P = 0.013) and basic fibroblast growth factor (bFGF) (25.9 vs. 9.5 pg/ml, P = 0.027) in blister fluid than patients without MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9 pg/ml, P = 0.024) and bFGF (15.8 vs. 31.9 pg/ml, P = 0.006) than non-survivors. In serum, survivors had higher levels of vascular endothelial growth factor (VEGF) (152.2 vs. 14.7 pg/ml, P = 0.012) and lower levels of IL-6 (38.5 vs. 91.1 pg/ml, P = 0.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did not correlate with the serum levels., Conclusions: Cytokine responses in skin blister fluid in patients with sepsis differed from those in healthy controls., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: The present study assessed the effect of smoking on clinical, microbiological and immunological parameters in an experimental gingivitis model., Material and Methods: Twenty-four healthy dental students were divided into two groups: smokers (n = 10); and nonsmokers (n = 14). Stents were used to prevent biofilm removal during brushing. Visible plaque index (VPI) and gingival bleeding index (GBI) were determined 5- on day -7 (running phase), baseline, 21 d (experimental gingivitis) and 28 d (resolution phase). Supragingival biofilm and gingival crevicular fluid were collected and assayed by checkerboard DNA-DNA hybridization and a multiplex analysis, respectively. Intragroup comparison was performed by Friedman and Dunn's multiple comparison tests, whereas the Mann-Whitney U-test was applied for intergroup analyses., Results: Cessation of oral hygiene resulted in a significant increase in VPI, GBI and gingival crevicular fluid volume in both groups, which returned to baseline levels 7 d after oral hygiene was resumed. Smokers presented lower GBI than did nonsmokers (p < 0.05) at day 21. Smokers had higher total bacterial counts and higher proportions of red- and orange complex bacteria, as well as lower proportions of Actinomyces spp., and of purple- and yellow-complex bacteria (p < 0.05). Furthermore, the levels of key immune-regulatory cytokines, including interleukin (IL)-8, IL-17 and interferon-γ, were higher in smokers than in nonsmokers (p < 0.05)., Conclusion: Smokers and nonsmokers developed gingival inflammation after supragingival biofilm accumulation, but smokers had less bleeding, higher proportions of periodontal pathogens and distinct host-response patterns during the course of experimental gingivitis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Despite investigative efforts to identify the levels of different types of cytokines in the peri-implant crevicular fluid (PICF), the efficacy of these biomarkers in assisting the diagnosis of peri-implantitis is still undetermined. This systematic review aimed to answer the following question: "Could cytokine levels in the PICF be used to distinguish between healthy implants and implants with peri-implantitis?", Material and Methods: This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE and EMBASE databases were searched from 1990 up to and including March 2015, using MeSH terms and other keywords. Additional publications were searched using a hand search of reference lists of relevant studies. Titles and abstracts were screened and papers that fulfilled eligibility criteria were assessed., Results: Out of 1212 titles, 18 studies reporting the levels of nine different cytokines were included. Proinflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, IL-17 and tumor necrosis factor-α) were the cytokines studied most commonly, followed by anti-inflammatory cytokines (IL-4 and IL-10), osteoclastogenesis-related cytokines (RANKL) and chemokines (IL-8). Nine studies reported statistically significantly higher levels of proinflammatory cytokines in the PICF of implants with peri-implantitis than in the PICF of healthy implants. Most studies did not find any significant differences in the PICF levels of anti-inflammatory cytokines and RANKL between healthy implants and implants with peri-implantitis. IL-8 was the only chemokine studied and its levels did not differ significantly between healthy and diseased implants. The studies differed greatly in the manner in which they reported the results (e.g. concentrations or total amounts) and in the exclusion of confounders, such as smoking., Conclusion: The results of this systematic review indicate moderate evidence in the literature to support that implants with peri-implantitis present higher levels of proinflammatory cytokines in the PICF than do healthy implants. Evidence regarding the PICF levels of anti-inflammatory cytokines, osteoclastogenesis-related cytokines and chemokines as possible predictors of peri-implantitis is too limited., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the present study was to investigate how heavy smoking influences the clinical, microbiological, and host-response characteristics in peri-implant sulcus fluid of patients with healthy dental implants., Methods: A total of 29 individuals with 74 dental implants were included in the present study; 20 implants were in heavy smokers and 54 were in non-smokers. The modified gingival index, modified plaque index, and probing pocket depth were evaluated. Periodontopathogenic bacteria Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis were evaluated, together with the total bacterial load. Peri-implant sulcus fluid samples were analyzed for the quantification of interleukin-8, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α., Results: No significant differences in the clinical parameters evaluated were found between the groups, although smokers had poorer peri-implant parameters. Among the smokers, subgingival microbiota was composed of a greater number of periodontal pathogens; these differences were not statistically significant. Smokers showed a greater expression of interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α, but interleukin-8 was slightly higher among non-smokers, but not significantly., Conclusions: Although smokers presented deeper probing depths, bleeding on probing, and peri-implant microbiota composed of a greater number of periodontal pathogens than in non-smoking patients, these data did not show significant differences. In the present study, and in relation to the samples analyzed, smoking alone did not influence the immunological and microbiological parameters in dental implants with healthy peri-implant tissues. Further studies with larger samples are required to better evaluate the influence of smoking on dental implants., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: We aimed to detect the role of obesity on the healing response to periodontal therapy in terms of serum lipids, C-reactive protein (CRP) and both serum and gingival crevicular fluid adipocytokines., Material and Methods: Thirty patients with periodontitis with (CPO) (n = 15) and without (n = 15) obesity and 15 healthy controls were included. Serum high-density lipoprotein, low-density lipoprotein, triglyceride, CRP levels and levels of adiponectin, interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 were evaluated before and 3 mo after initial periodontal therapy. Clinical periodontal measurements were also recorded at baseline and 3 mo., Results: Periodontal parameters improved significantly in both periodontitis groups with or without obesity (p < 0.05) with no significant difference in terms of gain clinical attachment level (p > 0.05) and change in numbers of sites with probing depth ≥ 4 mm. High-density lipoprotein significantly increased in both groups (p > 0.05). CRP decreased significantly solely in the normal weight group. IL-6, IL-10 and TNF-α levels in gingival crevicular fluid improved significantly based on therapy in both groups (p < 0.05). Only TNF-α decreased significantly in the CPO, while adiponectin and IL-10 in addition to TNF-α improved significantly in the group of patients with periodontitis without obesity., Conclusion: Patients with CPO respond to periodontal therapy as well as the non-obese controls. This similar response is accompanied with consistent adipokine levels in gingival crevicular fluid. However, obesity affects the CRP and serum adipocytokine levels in response to therapy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Macrophages are involved in the full processes of tissue healing or regeneration and play an important role in the regeneration of a variety of tissues. Although recent evidence suggests the role of different macrophage phenotypes in adipose tissue expansion, metabolism, and remodeling, the spectrum of macrophage phenotype in the adipose tissue engineering field remains unknown. The present study established a rat model of adipose tissue regeneration using a tissue engineering chamber. Macrophage phenotypes were assessed during the regenerative process in the model. Neo-adipose tissue was generated 6 weeks after implantation. Macrophages were obvious in the chamber constructs 3 days after implantation, peaked at day 7, and significantly decreased thereafter. At day 3, macrophages were predominantly M1 macrophages (CCR7+), and there were few M2 macrophages (CD206+). At day 7, the percentage of M2 macrophages significantly increased and remained stable at day 14. M2 macrophages became the predominant macrophage population at 42 days. Enzyme-linked immunosorbent assay demonstrated transition of cytokines from pro-inflammatory to anti-inflammatory, which was consistent with the transition of macrophage phenotype from M1 to M2. These results showed distinct transition of macrophage phenotypes from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 in adipose tissue regeneration in our tissue engineering model. This study provides new insight into macrophage phenotype transition in the regeneration of adipose tissue., (© 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Influenza A virus (IAV)-induced severe disease is characterized by infected lung epithelia, robust inflammatory responses and acute lung injury. Since type I interferon (IFNαβ) and type III interferon (IFNλ) are potent antiviral cytokines with immunomodulatory potential, we assessed their efficacy as IAV treatments. IFNλ treatment of IAV-infected Mx1-positive mice lowered viral load and protected from disease. IFNα treatment also restricted IAV replication but exacerbated disease. IFNα treatment increased pulmonary proinflammatory cytokine secretion, innate cell recruitment and epithelial cell death, unlike IFNλ-treatment. IFNλ lacked the direct stimulatory activity of IFNα on immune cells. In epithelia, both IFNs induced antiviral genes but no inflammatory cytokines. Similarly, human airway epithelia responded to both IFNα and IFNλ by induction of antiviral genes but not of cytokines, while hPBMCs responded only to IFNα. The restriction of both IFNλ responsiveness and productive IAV replication to pulmonary epithelia allows IFNλ to limit IAV spread through antiviral gene induction in relevant cells without overstimulating the immune system and driving immunopathology. We propose IFNλ as a non-inflammatory and hence superior treatment option for human IAV infection., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy., Methods: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated., Results: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups., Conclusion: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background and Objective: The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites., Material and Methods: This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid., Results: The levels of IL-1β, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1β increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1β decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1β, IL-6 and TNF-α were closely correlated with each other., Conclusion: This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Limited cell numbers in umbilical cord blood (UCB) grafts present a major impediment to favorable outcomes in adult transplantation, largely related to delayed or failed engraftment. The advent of UCB transplantation (UCBT) using two grafts successfully circumvents this obstacle, despite the engraftment of only one unit. Preclinical models suggested that the addition of UCB T cells at the time of transplant can enhance engraftment. We tested whether ex vivo activation by CD3/CD28 costimulation and expansion of T cells from a single UCB graft would be safe and feasible in adults with advanced hematologic malignancies, with an overall objective of optimizing engraftment in single unit UCBT. In this phase 1 study, recipients of single UCB units were eligible if the unit was stored in two adequate fractions. Dose limiting toxicity was defined as grade 3 or grade 4 GVHD within 90 days of UCBT. Four patients underwent UCBT; all were treated at the first dose level (10(5) cells/kg). At the 10(5) cells/kg dose level two subjects experienced grade 3 intestinal GVHD, thus meeting stopping criteria. For three subjects, neutrophil engraftment was early (12, 17, and 20 days), while one subject experienced primary graft failure. We observed early donor T cell trafficking and found that expanded T cells produced supraphysiologic levels of cytokines relevant to engraftment and to lymphoid differentiation and function. Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD., (© 2016 Wiley Periodicals, Inc.)

Purpose: Recently sodium alginate (SA)-poly-l-ornithine (PLO) microcapsules containing pancreatic β-cells that showed good morphology but low cell viability (<27%) was designed. In this study, two new polyelectrolytes, polystyrenic sulfonate (PSS; at 1%) and polyallylamine (PAA; at 2%) were incorporated into a microencapsulated-formulation, with the aim of enhancing the physical properties of the microcapsules. Following incorporation, the structural characteristics and cell viability were investigated. The effects of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA), on microcapsule morphology, size, and stability as well as β-cell biological functionality was also examined., Methods: Microcapsules were prepared using PLO-PSS-PAA-SA mixture and two types of microcapsules were produced: without UDCA (control) and with UDCA (test). Microcapsule morphology, stability, and size were examined. Cell count, microencapsulation efficiency, cell bioenergetics, and activity were also examined., Results: The new microcapsules showed good morphology but cell viability remained low (29% ± 3%). UDCA addition improved cell viability post-microencapsulation (42 ± 5, P < 0.01), reduced swelling (P < 0.01), improved mechanical strength (P < 0.01), increased Zeta-potential (P < 0.01), and improved stability. UDCA addition also increased insulin production (P < 0.01), bioenergetics (P < 0.01), and decreased β-cell TNF-α (P < 0.01), IFN-gamma (P < 0.01), and IL-6 (P < 0.01) secretions., Conclusions: Addition of 4% UDCA to a formulation system consisting of 1.8% SA, 1% PLO, 1% PSS, and 2% PAA enhanced cell viability post-microencapsulation and resulted in a more stable formulation with enhanced encapsulated β-cell metabolism, bioenergetics, and biological activity with reduced inflammation. This suggests potential application of UDCA, when combined with SA, PLO, PSS, and PAA, in β-cell microencapsulation and diabetes treatment. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:501-509, 2016., (© 2016 American Institute of Chemical Engineers.)

Background: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium., Methods: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated., Results: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR., Conclusion: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background and Objective: Based on lipopolysaccharide (LPS) antigenicity, different Aggregatibacter actinomycetemcomitans serotypes have been described. Serotype b strains have demonstrated a stronger capacity to trigger cytokine production on dendritic cells (DCs). As DCs regulate the development of T-lymphocyte lineages, the objective of this investigation was to study the response of T lymphocytes after being stimulated with autologous DCs primed with different bacterial strains belonging to the most prevalent serotypes of A. actinomycetemcomitans in humans: a-c., Material and Methods: Human DCs were primed with increasing multiplicity of infection (10(-1) -10(2) ) or the purified LPS (10-50 ng/mL) of A. actinomycetemcomitans serotypes a-c and then used to stimulate autologous naïve CD4(+) T lymphocytes. The T-helper (Th) type 1, Th2, Th17 and T-regulatory transcription factors T-bet, GATA-3, RORC2 and Foxp3, which are the master-switch genes implied in their specific differentiation, as well as T-cell phenotype-specific cytokine patterns were quantified by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, the intracellular expression of T-bet/interferon-γ, GATA-3/interleukin-4, RORC2/interleukin-17A and Foxp3/transforming growth factor-β1 was analysed by double staining and flow cytometry., Results: All the A. actinomycetemcomitans serotypes led to T-lymphocyte activation; however, when T lymphocytes were stimulated with DCs primed with the A. actinomycetemcomitans serotype b strain or their purified LPS, higher levels of Th1- and Th17-associated transcription factors and cytokines were detected compared with similar experiments with the other serotypes., Conclusion: These results demonstrate that serotype b of A. actinomycetemcomitans has a higher capacity of trigger Th1 and Th17 phenotype and function and it was demonstrated that their LPS is a more potent immunogen compared with the other serotypes., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Infections by Helicobacter can cause the stimulation of sophisticated immune response in mucosal immunity. Among the different lymphocytes, Th17 plays an important role in the defense against H. pylori and may cause gastritis and peptic ulcer due to the increased activation of Th17 and cytokine changes., Aim: To find a relationship between Th17 and IL-17A, IL-21, IL-22, IL-23, TGF-β in the patients with H. pylori infection having signs including gastritis and peptic ulcer., Methods: A total of 36 samples from the patients [24 Hp+ and 12 Hp- cases] with dyspepsia symptoms were collected. The percentage of Th17 was measured by flow cytometry. The levels of Th17-associated cytokines in the sera and supernatants of peripheral blood mononuclear cells (PBMCs) which were stimulated with the H. pylori antigen, phytohemagglutinin (PHA), or Dynabeads were measured by ELISA., Results: Patients were divided into two groups of having either H. pylori infected (peptic ulcer, gastritis (mild, moderate)) or being uninfected. The percentage of Th17 in the patients with peptic ulcer and gastritis was significantly higher than their uninfected counterparts (p ≤ .001). The serum levels of IL-17A, IL-23, and TGF-β in the peptic ulcer and gastritis groups were significantly higher compared with the corresponding levels in the uninfected population (p < .05). A significant association of TGF-β, IL-21, and Th17 was observed with low levels of IL-17A in the mild gastritis patients (p < .05). Significantly higher levels of IL-22, IL-17A, IL-23, and higher Th17 frequencies were detected in the moderate gastritis patients, as compared with the uninfected patients (p ≤ .001)., Conclusion: It can be concluded that among the cytokines associated with Th17, the two cytokines of IL-21 and TGF-β play a more critical role in peptic ulcer and gastritis in the individuals infected with H. pylori. Furthermore, inflammation varies depending on the type of the cytokine and its secreted level., (© 2015 John Wiley & Sons Ltd.)

Background and Objectives: Probiotics create a biofilm and protect the oral tissues against the action of periodontal pathogenic bacteria. The aim of this study was to evaluate the effects of the oral probiotic Lactobacillus reuteri Prodentis upon the peri-implant health of edentulous patients with dental implants and peri-implant mucositis, establishing comparisons vs implants without peri-implant disease., Material and Methods: A double-blind, placebo-controlled, prospective cross-over study was made. The patients were all edentulous and were divided into two groups, (A) no peri-implant disease, and (B) peri-implant mucositis affecting one or more implants. Patients with peri-implantitis were excluded. The dosage was one tablet every 24 h over 30 d. All patients in both groups initially received the oral probiotic Lactobacillus reuteri Prodentis, followed by placebo. Patients started with probiotic treatment during 30 d, followed by a 6 mo washout period and the administration of placebo for the same period. The following parameters were studied: crevicular fluid volume, modified plaque index, probing depth, modified gingival index, and concentrations of interleukin 1β, interleukin 6 and interleukin 8., Results: A total of 77 implants were evaluated in 34 patients. Group A involved 22 patients with 54 implants without peri-implant alterations, and group B, 12 patients with mucositis affecting one or more implants (23 implants). After treatment with the probiotic, both the patients with mucositis and the patients without peri-implant disease showed improvements in the clinical parameters, with reductions in cytokine levels. In contrast, no such changes were observed with placebo., Conclusions: After treatment with the probiotic Lactobacillus reuteri in patients with implants presenting mucositis, the clinical parameters improved, and the cytokine levels decreased - in contraposition to the observations in the placebo group. Probiotic administration may be regarded as a good alternative for both the treatment of peri-implant mucositis and its prevention, as it also improved clinical parameters in the healthy individuals. Further studies involving larger patient series are needed regarding the effects of probiotics upon peri-implant health., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Endoplasmic reticulum (ER) stress is the cell response that activates the unfolded protein response (UPR) pathway in a variety of conditions, such as inflammation and bone metabolism. The UPR may be associated with the pathogenesis of periodontal disease because the disease is inflammatory in nature, and alveolar bone resorption is a characteristic feature of the disease. However, the relationship between ER stress and alveolar bone resorption observed in periodontal disease remains elusive., Material and Methods: C57BL/6 mice were orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, in the presence or absence of a chemical chaperone, 4-phenylbutyrate (4-PBA). The gene expression of UPR-related molecules and cytokines in gingival tissues were analyzed using real-time polymerase chain reaction, and alveolar bone resorption and osteoclast numbers were evaluated histologically. The in vitro effect of 4-PBA on the differentiation of mouse bone marrow cells induced by receptor activator of nuclear factor-κB ligand in the presence of macrophage colony-stimulating factor was analyzed., Results: The gene expression levels of UPR-related molecules and proinflammatory cytokines and alveolar bone resorption were significantly increased in P. gingivalis-administered mice. UPR-related gene expression and alveolar bone resorption were significantly suppressed by the administration of 4-PBA. However, no effect of 4-PBA was observed for proinflammatory cytokine expression in gingival tissues. Osteoclastic differentiation of bone marrow cells was also suppressed by 4-PBA with a concomitant reduction in the gene expression of cathepsin K and tartrate-resistant alkaline phosphatase genes., Conclusion: ER stress induced by oral administration of P. gingivalis is involved in alveolar bone resorption independent of inflammatory cytokines in mice., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim was to assess clinical inflammatory parameters, cytokine levels and bacterial counts in samples from implant crevicular fluid in cases with untreated peri-implantitis., Material and Methods: Several bacterial species known to up-regulate pro-inflammatory cytokines have been associated with peri-implantitis. The Luminex magnet bead technology was used to study cytokines in crevicular fluid. The checkerboard DNA-DNA hybridization method was used to study bacterial counts in samples from 41 implants (41 individuals)., Results: Profuse bleeding and suppuration was found in 25/41 (61.0%) of the implants. The reliability of duplicate cytokine processing was high. In the presence of profuse bleeding, higher pg/ml levels of IL-1β (p = 0.02), IL-8 (p = 0.04), TNF-α (p = 0.03) and VEGF (p = 0.004) were found. Higher concentrations of IL-1β were found in the presence of suppuration, and if Escherichia coli (p = 0.001) or Staphylococcus epidermidis (p = 0.05) could be detected., Conclusion: Profuse bleeding and/or suppuration in untreated peri-implantitis can be associated with higher concentrations of IL-1β, IL-8, TNF-α and VEGF in peri-implant crevicular fluid. A higher concentration of IL-1β in peri-implant crevicular fluid was found in samples that were positive for E. coli or S. epidermidis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of this study was to determine whether the concentration of cytokines in the gastric fluid at birth was associated with chorioamnionitis or funisitis and with the white blood cell counts of very premature newborns., Methods: We retrieved gastric fluid from 27 preterm infants with a gestational age of <29 weeks within 1 h of birth and used enzyme-linked immunosorbent assay to measure the concentrations of interleukin (IL)-1beta, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IL-8 and growth-related oncogene (Gro)-alpha. The presence of histologic chorioamnionitis or funisitis in the placentas and the highest white blood cell count of the infants during the first week of life were compared to the cytokine concentrations., Results: Gastric fluid concentrations of IL-1beta, ENA-78, IL-8 and Gro-alpha were strongly associated with chorioamnionitis and funisitis. In addition, chorioamnionitis and funisitis and gastric aspirate cytokine levels were associated with the highest white blood cell counts of the infants during the first week of life., Conclusion: This study suggests that levels of inflammatory cytokines in the gastric fluid of premature infants at birth can be used to assess the exposure of the infants to antenatal inflammation., (©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)