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Uterine leiomyomas (UL) are benign uterine tumors. Hypertrophic increase in muscle mass in LM is accompanied by development of vascular networks, which are regulated by the balance of pro-angiogenic factors, e.g., VEGF-A. Moreover, a number of inflammatory molecules exert pro-angiogenic effects, especially, IL-1β, IL-8, etc. The spectrum of their activity may overlap, being regulated by other cytokines. The aim of our work was to assess serum concentrations of cytokines actively involved in vascular network growth in the patients with multiple uterine fibroids, as compared with data obtained in conditionally healthy women. The survey included 178 females: 89 women (23-60 years old) with uterine fibroids, and 89 conditionally healthy age-matched women (22-61 years old). The levels of TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10 and VEGF-A were detected by ELISA technique (Vector-Best, Russia). Statistical analysis was carried out using the IBM SPSS Statistics 23 (USA). Serum levels of IL-6, TNF and IL-8, were higher among patients compared with healthy women. The dependence of VEGF level on the number of myoma nodes has been established: VEGF serum level was higher in patients with multiple tumor nodes. In healthy women, an increase in TNFα level showed direct correlation with higher serum level of IL-6. Correlation with VEGF level was weakly negative. In leiomyoma, these relationships persist for IL-6, IL-8, VEGF levels. The obtained data are of practical importance not only as potential prognostic criteria for development of the uterine myoma at preclinical stage, but also as additional laboratory indexes for differential diagnostics, in particular when discerning uterine leiomyoma, the most common benign myomatous tumor of uterus, from malignant uterine leiomyosarcomas.

Community-acquired pneumonia (CAP) is a common respiratory disease in children. This prospective cohort study of 110 children with CAP and 100 healthy children investigated the relationship between the levels of vitamin A, D and E and inflammatory markers, such as tumour necrosis factor (TNF-a), interleukin-1 (IL-1), interleukin-10 (IL-10), neutrophils (NE) and C-reactive protein (CRP), in CAP. The haemoglobin, leukocyte concentration, NE, monocytes and CRP concentration in the CAP group showed significant differences (P < 0.05). The levels of vitamin A, D and E in the CAP group were lower than those in the control group, while the levels of TNF-a and IL-1 were higher than in the control group; the differences were statistically significant (P < 0.05). The IL-10 levels showed no significant differences (P > 0.05). Pearson analysis revealed that the vitamin A, D and E levels were all correlated with the TNF-a, IL-10 and CRP levels (P < 0.05). The vitamin A, D and E levels of the CAP children were lower than those of the healthy children. Thus, the content of fat-soluble vitamins is correlated with the secretion of TNF-a and IL-10. The research provides a new direction for the prevention, diagnosis and treatment of CAP.

Multipotent mesenchymal stromal cells (MSC) play an increasing role in the treatment of immune-mediated diseases and inflammatory processes. They regulate immune cells via cell-cell contacts and by secreting various anti-inflammatory molecules but are in turn influenced by many factors such as cytokines. For MSC culture, platelet lysate (PL), which contains a variety of cytokines, is a promising alternative to fetal bovine serum (FBS). We aimed to analyze if PL with its cytokines improves MSC immunoregulatory characteristics, with the perspective that PL could be useful for priming the MSC prior to therapeutic application. MSC, activated peripheral blood mononuclear cells (PBMC) and indirect co-cultures of both were cultivated in media supplemented with either PL, FBS, FBS+INF-g or FBS+IL-10. After incubation, cytokine concentrations were measured in supernatants and control media. MSC were analyzed regarding their expression of immunoregulatory genes and PBMC regarding their proliferation and percentage of FoxP3+ cells. Cytokines, particularly IFN-g and IL-10, remained at high levels in PL control medium without cells but decreased in cytokine-supplemented control FBS media without cells during incubation. PBMC released IFN-g and IL-10 in various culture conditions. MSC alone only released IFN-g and overall, cytokine levels in media were lowest when MSC were cultured alone. Stimulation of MSC either by PBMC or by PL resulted in an altered expression of immunoregulatory genes. In co-culture with PBMC, the MSC gene expression of COX2, TNFAIP6, IDO1, CXCR4 and MHC2 was upregulated and VCAM1 was downregulated. In the presence of PL, COX2, TNFAIP6, VCAM1, CXCR4 and HIF1A were upregulated. Functionally, while no consistent changes were found regarding the percentage of FoxP3+ cells, MSC decreased PBMC proliferation in all media, with the strongest effect in FBS media supplemented with IL-10 or IFN-g. This study provides further evidence that PL supports MSC functionality, including their immunoregulatory mechanisms. The results justify to investigate functional effects of MSC cultured in PL-supplemented medium on different types of immune cells in more detail. [ABSTRACT FROM AUTHOR]

Aim: investigate the possible anti-psoriatic effect of ivermectin in mice based on observational and histopathological outcomes and biomarkers. Methods: Sixty male Swiss Albino Mice were divided into six groups (Groups I-VI); each group contained ten mice with shaved dorsal skin. The clinical, pathological, and laboratory effects were measured. Results: Topical Ivermectin significantly decreased vascular endothelial growth factor levels. At the same time, the combination of ivermectin plus Clobetasol showed a more significant reduction in tumor necrosis factor-alpha (TNF-α) and Interleukin-17 (IL-17) levels. Regarding the Interleukin-10 (IL-10) level, the Ivermectin and Ivermectin/Clobetasol combination groups showed a significant increase in IL-10. Conclusion: Topical Ivermectin's anti-psoriasis activity increases IL-10 levels and could be used efficiently to alleviate psoriatic symptoms. Its combination treatment with Clobetasol holds promise for the management of psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 infection (COVID-19) induces dysregulated production of pro- and anti-inflammatory cytokines, called the cytokine storm, leading to the development of severe pneumonia and ARDS. We aimed to examine the dynamic cytokine response on different days of the disease in adult COVID-19 patients. Methodology: Our study included 142 patients (with SARS-CoV-2 PCR-positive nasopharyngeal samples) with varying disease severity and admitted on different days of the disease. We examined the presence and mean levels of TNF-a and IL-10 and did a correlation and logistic regression analysis. Results: TNF-a levels were high in all patients, with mean levels being the highest on day 5 of the disease. IL-10 was high only in a quarter of the patients. The levels of IL-10 were also the highest on day 5, which was significantly different from the mean levels on the other days of the disease. Average IL-10 levels were not any higher than the normal range on the other days. We found a significant positive correlation between the levels of TNF-a and IL-10 during the first week of the infection. In the second week, the positive correlation was no longer significant, and starting from day 10, there was even a slight negative correlation. IL-10 level increase showed prognostic significance for severe, but not the critical forms of the disease. Conclusions: The uncontrolled immune response to SARS-CoV-2 in the second week of the disease can be the result of dysregulated production of endogenous anti-inflammatory cytokines. This leads to a severe disease course and a possible unfavorable outcome. [ABSTRACT FROM AUTHOR]

Among the cancers that impacts men, prostate cancer considerably raises deaths for males around the world. Persons with tumours can have a localized or advanced form of the illness. The present study aimed to determining the relationship between the level of cytokines (IL-10 and TNF-a) and PSA in the sera of patients and compared it with healthy. A case control study consist of three group included was in this study. The first group involves 50 patients with PC were observation in Al-Amal Oncology Hospital in the period from April 2021 to April 2022 under the supervision of oncology specialists was included in this study. Second group consist of 30 patients. They have benign hyper plaisa (BHP), this group has been collected from urosergical department . Third group was include 20 healthy volunteers (non prostate cancer and non BHP). Prostate specific antigen (PSA) was measured by mini – VIDAS device using kit supplied by Biomerieux – France. IL-10 and TNF-a levels were measured by ELISA technique using kit supplied by CAUSABIO – China. Results of the present study showed the 60–69 years age group scored highest percentage in benign (56.7%), malignant (54.0%), compared to control (healthy) (50.0%), while > 69 years scored least percentage in these groups (3.3%, 14.0%, and 25.0%) respectively with significant different (p< 0.05). Additionally, the IL-10 and PSA scored highest mean levels in the malignant group (1.22 ± 0.23 and 27.66 ± 6.31), while TNF-a scored highest mean levels in a benign group (0.30 ± 0.11). The least mean level of IL-10 was in healthy (0.42 ± 0.15), TNF-a in malignant (0.23 ± 0.03), and PSA in benign (6.73 ± 1.36). Finally, there is a significant difference among age groups and PSA, IL-10, and TNF-parameters. We concluded the PSA, TNF-a and IL-10 parameters are play important roles in pathogenesis patients with prostate cancer. PCa is high prevalence in elderly population. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the levels of circulating inflammatory factors CRP, IL-6, IL-10 and TNF-a based on the literature review. This study also examined the influence of single nucleotide polymorphism (SNP) sites on the susceptibility of abdominal aortic aneurysm (AAA) using meta-analysis and intended to provide additional information on pathogenesis of AAA research. Methods: Electronic databases including PubMed and Web of Science were systemically searched to collect the information on AAA, inflammatory factors such as CRP, IL-6, IL-10, TNF-a and the SNP sites for data extraction. Altogether six SNPs in four genes (rs3091244, CRP; rs1800947, CRP; rs1205, CRP; rs1800795, IL-6; rs1800896, IL-10; and rs1800629, TNF) were assessed. Results: This study enrolled altogether 41 relevant investigations involving 9,007 AAA patients to carry out meta-analysis. According to pooled analysis, circulating CRP and IL-6 levels were shown to be related to the AAA, while plasma IL-10 and TNF-a levels were not associated with AAA. The circulating CRP level standard mean difference (SMD) was 0.30 (95% confidence interval (CI): 0.17-0.43), the IL-6 level SMD was 0.34 (95% CI: 0.20-0.49), the IL-10 level SMD was -0.01 (95% CI: -0.09-0.06), and the TNF-a level SMD was 0.09 (95% CI: 0.00-0.19). Similarly, the odds ratio (OR) of rs3091244 (CRP) under the recessive gene model was 1.70 (95% CI: 1.13-2.57). In addition, individuals with A and T mutant genes at locus rs3091244 might have a higher tendency of AAA susceptibility than those with C allele. Consecutively, the OR was 0.91 (95% CI: 0.51-0.97) for rs1800795 (IL-6) locus in the allele model, and individuals with G mutant gene at locus rs1800795 (IL-6) might be less susceptible to AAA than those with C allele. Meanwhile, the rs1800896 (IL-10) locus had a positive association under the five statistical models, and individuals with A mutant gene at locus rs1800896 might have a higher susceptibility to AAA than those with G allele. Nevertheless, the rs1800947 (CRP), rs1205 (CRP), and rs1800629 (TNF) loci did not have positive correlation under the five statistical models, with no statistical significance. The results indicate that the gene polymorphisms at rs1800629, rs1800947, and rs1205 loci were not related to the AAA susceptibility. Conclusions: Gene polymorphisms in certain known inflammatory mediators related to AAA susceptibility might serve as potential predictive biomarkers for clinical applications. Moreover, SNP of inflammatory mediators relevant to abdominal aortic aneurysmal formation and progression need extensive investigations to confirm these results. [ABSTRACT FROM AUTHOR]

The pathophysiology of pain in patients suffering from rotator cuff (RC) tendinopathy or tears has been examined in various ways. Several molecules from tissue samples taken from the subacromial bursa, supraspinatus tendon, glenohumeral joint fluid, and synovium as well as from peripheral blood have been investigated. This article explores these studies, the assessed biomarkers, and groups their results according to the status of tendon integrity (tendinopathy or tear). Through a structured PubMed database search, 9 out of 658 articles were reviewed. Interleukins, mostly IL-1b and its antagonist, IL-1ra, matrix Metalloproteinases (MMPs), the vascular endothelial growth factor (VEGF) and TNF-a are biomarkers directly searched for correlation to pain level. Most studies agree that IL-1b is directly positively correlated to the degree of pain in patients with RC tendinopathy, especially when the examined sample is taken from the subacromial bursa. VEGF, and TNF-a have been related to shoulder pain preoperatively and TNF-a has also been linked with sleep disturbance. Further studies pointing to more biomarkers taken from the subacromial bursa or tendon directly relating to pain degree are warranted. [ABSTRACT FROM AUTHOR]

The natural stilbene compound resveratrol (RSV) was extracted and purified locally from the black grape skin (Vitis vinifera) cultivated in Iraq. Cultures of human peripheral lymphocytes were obtained from the blood samples of patients with and without lymphoma to be treated with RSV at different concentrations. Three RSV concentration levels were subjected to isolated lymphocytes from blood samples of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and without lymphoma to estimate the change in TNF-a and IL-10. Resveratrol seemed to differently affect cytokines level in normal and lymphoma lymphocytes in relation to its concentration. The lowest resveratrol concentration (50 µg/ml) decreased TNF-a levels for patients without lymphoma and all NHL patients in contrast to the HL sample. Treating normal lymphocytes with a higher dose (1000 µg/ml) might elevate the levels of TNF-a in almost all samples. There was an inverse relationship between both cytokines in most treatments; with the increase in TNF-a level, there was a decrease in IL-10 level except in HL and normal lymphocytes treatment. The locally purified resveratrol could serve as a multi-target drug that modulates the immune system to improve body defense in patients suffering from lymphoma and in patients without lymphoma by altering cytokine levels in response to different resveratrol concentrations in a different manner. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a positive-sense singlestranded RNA virus from the genus Betacoronavirus causes COVID-19 (coronavirus disease 2019). According to daily reports issued by the Iraqi Ministry of Health, the SARS-COV-2 was firstly detected in Al-Najaf city in February 2020 and identified in the Central Public Health Laboratory (CPHL) in Baghdad, Iraq. The outcomes of this study were based on 100 nasopharyngeal swaps and venous blood samples from hospitalized patients in Al-Kindy and CPHL. Patients were assigned to five groups (Asymptomatic, Mild, Moderate, Severe, and Deceased) based on disease severity as indicated by World Health Organization (WHO). The positive samples were identified by real-time quantitative polymerase chain reaction (RT-PCR) and subjected to some liver enzyme assays and interleukins measurements, and the correlation with the genetic sequence was determined by Illumina Miseq technology. Liver enzymes levels of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) showed statistically significant differences, especially between the deceased groups. Interleukins (IL-10, IL-18, and TNF-a) significantly differed among groups. This study revealed that three isolates belonging to the original strain isolated from Wuhan (A19) and characterized by their virulence caused severe symptoms and led to admission to isolation hospitals and intensive care units, and the last two isolates of (UK alpha V1) appeared in Iraq in early 2021. These strains which were less virulent than the Wuhan strain spread faster and appear in moderate and asymptomatic patients. [ABSTRACT FROM AUTHOR]

Lactobacillus fermentum PL9988 was isolated from an elderly person over 80 years of age living in a Korean longevity village. Results from a previous study showed various characteristics of L. fermentum PL9988 as a probiotic, including resistance to acid and bile acid, immune-enhancing activity, adhesiveness to the intestinal cell line Caco-2, inhibition of various intestinal pathogens, antioxidation activity, and susceptibility to antimicrobials. In this study, the binding activity of L. fermentum PL9988 to the intestine was confirmed in another human intestinal cell line, HT-29, and mouse intestinal cells. The anti-inflammatory activity of L. fermentum PL9988 was examined via both in vitro and in vivo experiments. Lactobacillus fermentum PL9988 increased the amount of IL-10 and decreased the amount of TNF-a in HT-29 cells treated with LPS. Similar results were observed in an in vivo experiment with BALB/c mice fed L. fermentum PL9988. Thus, results from the previous study and this study demonstrate the beneficial characteristics of L. fermentum PL9988 as a good probiotic with anti-inflammatory, antioxidative, and immune-enhancing activities in addition to improving intestinal health. [ABSTRACT FROM AUTHOR]

Background: Host genetic factors can influence susceptibility, morbidity and mortality from schistosomiasis. The study explored the association between single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10) and tumour necrosis factor alpha (TNF-a) promoter regions and susceptibility to Schistosoma haematobium infection. Methods: Urine specimens were collected from 361 primary school children aged 5-15 years from schistosomiasis endemic areas of Manicaland and Mashonaland central provinces. Schistosoma haematobium was diagnosed using the urine filtration method. Only 272 participants provided adequate blood for genotyping. Genotyping was performed using the amplification refractory mutation system-polymerase chain reaction. The association between IL-10 and TNF-a SNPs and S. haematobium infection was analysed using the chi-square test. Results: Schistosoma haematobium infection was confirmed in 26.8% of the participants. No significant difference in S. haematobium prevalence between men (51.6% of those infected) and women (48.4%) (X² = 0.008, df = 1, p = 0.928) was observed. The total IL-10 -1082 G, IL-10 -819 C and TNF-a -308G allele distribution between S. haematobium infected and uninfected participants was 50.7% and 51.5% (X² = 0.025, df = 1, p = 0.87), 54.3% and 60.6% (X² = 1.187, df = 1, p = 0.187) and 82.1% and 80.9% (X² = 0.099, df = 1, p = 0.753), respectively, and the differences were not significant. Conclusion: Interleukin-10 -1082 G/A, IL-10 -819 C/T and TNF-a -308 G/A SNPs were not significantly associated with susceptibility to S. haematobium infection. The prevalence of schistosomiasis is still in the moderate range and is similar in boys and girls. [ABSTRACT FROM AUTHOR]

Lower respiratory tract disease (LRT) a major public health problems with high mortality and one of the common causes of morbidity in children. Cytokines play a key role in the inflammatory process and pathogenesis of LRT disease. So the study aimed to detection the association between imbalance in pro- and anti-inflammatory biomarkers as cytokines (IL-6, TNF-á and IL-10) level and the development or progress some LRT disease such as bronchiolitis, bronchopneumonia and bronchial asthma. Case-control hospital study was performed of 100 patients with LRT disease in Baghdad Teaching Hospital in Baghdad city, Iraq with group of 30 healthy individual was used as control, the patients were divided according to types of disease into bronchiolitis 40 patients; bronchial asthma 38 patients and 22 patients suffering from pneumonia. The results revealed that percentage of male : female in both bronchiolitis and pneumonia was no significant different while the female were more than male in asthma and younger children more infected than aged children in LRT disease. The pro-inflammatory cytokine were increased in all diseases with higher level recorded in asthma then in bronchiolitis finally in pneumonia. In other hand the antiinflammatory cytokine appear that the asthma revealed high decreased then the bronchiolitis, finally the pneumonia. In conclusion, the imbalance in pro-inflammatory cytokine with increased their serum levels ,vs decreased the serum level of anti-inflammatory lead to persistence the inflammatory response and severity of respiratory disease. Also, the defect in cytokines level lead to increase the progression of LRT disease and can be consider as risk factor. [ABSTRACT FROM AUTHOR]

Aihong Meng,1 Xiaopeng Zhang,2 Siyu Wu,1 Mingxia Wu,1 Jing Li,1 Xixin Yan,1 Kamilla Kopec-Harding,3 Jiakai Wu41Respiratory Division, The Second Hospital of Hebei Medical University, 2Department of Thoracic Surgery, Hebei Province General Hospital, Shijiazhuang, Hebei, Peoples’ Republic of China; 3Centre for Musculoskeletal Research, 4Centre for Respiratory and Allergy, Institute of Inflammation and Repair, University of Manchester, Manchester, UKBackground: Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients’ sera.Objective and methods: Data from 66 COPD patients and 15 age-/sex-matched healthy controls were compared. Interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and CCL5 were measured in serum samples and culture media from peripheral blood mononuclear cells. The impact of sera on IL-10 and CCL5 expression in alveolar macrophage cell line (MH-S) was examined. The in vitro effects of SB203580 on lipopolysaccharide-induced inflammation were investigated.Results: Peripheral blood mononuclear cells from Global Initiative for Chronic Obstructive Lung Disease (GOLD) D patients produced more CCL5 and TNF-α, and less IL-10 compared to GOLD A–C patients. SB203580 treatment suppressed CCL5 and TNF-α and stimulated IL-10 production; however, the effect of SB203580 on IL-10 was lower in the COPD group. Culture of MH-S cells with COPD serum showed a significant increase in CCL5 and a significant decrease in IL-10 compared to healthy serum. This effect was not suppressed with SB203580 treatment.Conclusion: COPD serum has a potent proinflammatory effect on pulmonary cells. Inhibition of p38 phoshorylation had a limited effect in restoring impaired lymphocyte function and suppressing inflammation induced by COPD serum, implying important p38-independent inflammatory mechanisms in COPD. Keywords: COPD, p38MAPK inhibitor, macrophage, CCL5, TNF-α, IL-10

Background: Many factors contribute for viral clearance and response to antiviral therapy. Genetic polymorphisms of cytokines, chemokines, and their receptors can alter the immune response against Hepatitis C virus (HCV). Aim of the study: The aim of the current study is to assess single nucleotide polymorphism (SNP) in the promoter region of IL-10, TNF-α, IFN-ώ and TGF-β as predictors of response to combined Pegylated interferon a/ribavirin (PEG-IFN/RBV) therapy in chronic HCV infected Egyptian patients. Patients and methods: The study was conducted on 150 HCV infected patients and 100 apparently healthy control subjects. All patients were treated with PEG-IFN/RBV. They were classified according to their response to treatment. Genotyping of IL-10, TNF-α, IFN-ώ and TGF-β were performed on peripheral blood DNA using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and primer specific assays. Results: Overall, 83/150 (55.3%) patients achieved sustained virological response (SVR), whereas 67 (44.7%) did not. Age and BMI were significantly lower in patients who achieved SVR (P<0.05). IL-10 at site (±1082) GG genotype was associated with SVR where odds ratio was 1.98 with 95% confidence interval (1.34-3.65). None of the other genes showed a significant association with SVR. Conclusion: Analysis of IL-10 SNP at promoter site (±1082) could be used as a pretreatment predictor of response to combined PEG-IFN/RBV treatment. [ABSTRACT FROM AUTHOR]

El FNT-a y la IL-10 son citocinas reguladoras que intervienen en los procesos inmunológicos y actúan como mediadores proinflamatorios y antiinflamatorios, respectivamente. Se ha demostrado que los niveles de estos mediadores inciden en la susceptibilidad y en el curso de diferentes enfermedades infecciosas, alérgicas y autoinmunes. Se ha reportado un importante número de polimorfismos en la región promotora del gen correspondiente y algunos de ellos se han relacionado directamente con los niveles de expresión y producción de estas citocinas, en particular, en los nucleótidos de las posiciones -308 del gen de FNT-a y -1082, -819, -592 del gen de IL-10. Varios estudios han demostrado asociación de estos polimorfismos simples (SNP, single nucleotide polymorphisms) con la susceptibilidad y seriedad de este tipo de enfermedades. Este artículo de revisión presenta la síntesis de la relación de estos polimorfismos genéticos con la susceptibilidad y el curso de las enfermedades infecciosas, alérgicas y autoinmunes.TNF-a and IL-10 are regulatory cytokines that participate in the immune response acting either as pro-inflammatory or as anti-inflammatory mediators, respectively. It has been shown that the levels of these mediators influence the susceptibility and the outcome of different infectious, allergic and autoimmune pathologies. An important number of polymorphisms on the promoter region of the corresponding gene have been related with the levels of expression and synthesis of these cytokines, in particular the polymorphism on positions -308 of TNF-a and -1082, -819 and -592 of IL-10. Other studies have demonstrated the association of these single nucleotide polymorphisms (SNP) with the susceptibility and severity of this type of diseases. This review presents the synthesis of the relationship of these genetic polymorphisms with the susceptibility and evolution of infectious, allergic and autoimmune pathologies.

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease (JD) in cattle, has significant impacts on the livestock industry and has been implicated in the etiology of Crohn's disease. Macrophages play a key role in JD pathogenesis, which is driven by the manipulation of host immune mechanisms by MAP. A change in the macrophage microenvironment due to pathogenic or host-derived stimuli can lead to classical (M1) or alternative (M2) polarization of macrophages. In addition, prior exposure to antigenic stimuli has been reported to alter the response of macrophages to subsequent stimuli. However, macrophage polarization in response to MAP exposure and its possible implications have not been previously addressed. In this study, we have comprehensively examined monocyte/macrophage polarization and responsiveness to antigens from MAP-exposed and unexposed animals. At 3 years post-exposure, there was a heterogeneous macrophage activation pattern characterized by both classical and alternate phenotypes. Moreover, subsequent exposure of macrophages from MAP-exposed cattle to antigens from MAP and other mycobacterial species led to significant variation in the production of nitric oxide, interleukin-10 and tumour necrosis factor a. These results indicate the previously unreported possibility of changes in the activation state and responsiveness of circulating monocytes/macrophages from MAP-exposed cattle. [ABSTRACT FROM AUTHOR]

Experimental murine L. major infection is characterized by the expansion of distinct CD4+ T cell subsets. The Th1 response is related to production of IFN-g and resolution of infection, whereas Th-2 response with production of IL-4 and IL-10 and dissemination of infection. The objective of this study was to measure the circulating levels of IFN-g, IL-10 and TNF-a in patients with visceral leishmaniasis (VL) before, during and at the end of therapy and to examine the association between cytokine levels and activity of VL. Fifteen patients with VL were evaluated. The cytokine determinations were done by using the enzyme-linked immunoassay (ELISA) before, during and at the end of therapy. At baseline, we detected circulating levels of IFN-g in 13 of 15 patients (median = 60 pg/ml); IL-10 in 14 of 15 patients (median = 141.4 pg/ml); and TNF-a in 13 of 14 patients (median = 38.9 pg/ml). As patients improved, following antimonial therapy, circulating levels of IL-10 showed an exponential decay (y = 82.34 e–0,10367x, r = –0.659; p < 0.001). IFN-g was no longer detected after 7/14 days of therapy. On the other hand, circulating levels of TNF-a had a less pronounced decay with time on therapy, remaining detectable in most patients during the first seven days of therapy (y = 36.99-0.933x, r = –0.31; p = 0.05). Part of the expression of a successful response to therapy may, therefore, include reduction in secretion of inflammatory as well as suppressive cytokines. Since IL-10 and IFN-g are both detected prior to therapy, the recognized cellular immune depression seen in these patients may be due to biological predominance of IL-10 (type 2 cytokine), rather than lack of IFN-g (type 1 cytokine) production.

Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated. [ABSTRACT FROM AUTHOR]

Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 was determined using ELISA. Significant mother-to-child correlation was detected in cytokine-producing capacity at the age of 1 yr. TNF-α (P/I, SEB and LPS stimulation), IFN-γ (P/I and SEB), IL-5 (P/I and SEB) and IL-10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers’ than in children’s blood samples, except in the case of P/I and LPS-stimulated IL-8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL-5 (24 and 48 h) and IL-10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL-10 (48 h, P/I) responses and decreased IFN-γ/IL-5 ratio (24 h, P/I). In addition, the production of IFN-γ (24 and 48 h, P/I) and the IFN-γ/IL-5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine-producing capacity, our results suggest that children of atopic mothers express Th2-polarized cytokine pattern. [ABSTRACT FROM AUTHOR]

Aim: To compare the frequencies of cytokine and receptor molecule genotypes in patients with chronic periodontitis with the corresponding frequencies in a reference population and to study the relationship between periodontal disease severity and polymorphisms in the studied genes. Subjects and methods: CD14, IL-6, TNF- α, IL-10, IL-1 α, IL-1 β, and TLR-4 polymorphisms of 51 periodontitis patients were studied using polymerase chain reaction. The genotype frequencies in the periodontitis patients and a reference population ( n=178) were compared. Probing pocket depth (PD), periodontal attachment level (AL), and alveolar bone level (BL) were related to the genotypes. Results: No statistically significant differences could be found between the frequencies of the cytokine genotypes in the periodontitis patients and in the reference group. The extent of periodontal disease was higher in subjects with the T-containing genotype of CD14−260 and the GG genotype of IL-6−174 when compared with the extent in the rest of the group. Subjects carrying the composite genotype of the above two were most severely affected by periodontal disease. Conclusion: According to the present results, an evident association exists between the carriage of the T-containing genotype of CD14−260 and the GG genotype of IL-6−174 and the extent periodontal disease. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by autoimmune reactions against one's own widespread determinants. Many cytokines are involved in activity regulation and organ involvement in various autoimmune diseases. It is well known that some tissues maintain a very high »entry barrier« concerning the development of immune-mediated inflammation, which leads to the state of »immune privilege« through the generation of specialized microenvironment. There are different patterns of cytokine synthesis in particular autoimmune diseases such as rheumatoid arthritis, type I diabetes, systemic lupus erythematosus and multiple sclerosis, and worth stressing is the difference between cytokines as phenotype markers and cytokines as inflammation and tissue damage mediators. In most autoimmune diseases the balance between proinflammatory and antiinflammatory cytokines determines the extent and spread of inflammation and can lead to conspicuous clinical effects. In SLE patients, for instance, we observed a significant elevation of TNF-α and IL-10 in all, but especially in neurologic disease form. Understanding of the fundamental mechanisms of T cell differentiation control is the road to the strategy of cytokine phenotype modulation and prevention of tissue damage and autoimmune diseases, promoting naturally the protection from them. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether tumor necrosis factor a (TNF-a), transforming growth factor ß1 (TGF-ß1) and interleukin-10 (IL-10) polymorphisms are among the factors influencing the development of pemphigus. Whole blood from 20 patients with pemphigus and 24 control subjects was taken. Genomic DNA was obtained and cytokine genotyping for IL-10 (-1082 G/A; -819 C/T), TGFB1 (codon 10 C/T, codon 25 G/C) and TNFA (-308 G/A) was performed using the ARMS-PCR method. The distribution of IL-10 (-819) alleles was significantly different between the pemphigus and control groups (P=0.009). In particular, allele T was associated with the disease (OR 3.291, 95% CI 1.350-8.020). Similar results were observed when only pemphigus vulgaris (PV) patients were analyzed (P=0.012, OR 3.410, 95% CI 1.346-8.639). An increased frequency of the low producer IL-10 haplotype (-1082/-819 A/T) in patients with pemphigus compared with controls was observed (OR 2.714, 95% CI 1.102-6.685) and this association was also significant when only PV patients were considered (OR 2.667, 95% CI 1.043-6.816). There were no differences between patients and controls in the frequency of any other gene polymorphism analyzed. The increased frequency of the low producer IL-10 haplotype (-1082 /-819 A/T) suggest that the carriage of this haplotype might predispose to pemphigus or the high and intermediate producer haplotypes may be protective factors. The prevalence of the allele IL-10 (-819 T) in pemphigus patients cannot be explained by the current hypothesis, according to which a particular allele of the gene is associated with a different level of cytokine production and therefore affects the predisposition to a particular disease. However, this cytokine polymorphism might be linked to an unknown susceptibility factor. [ABSTRACT FROM AUTHOR]