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Aim: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. Methods: A nested, case–control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age‐matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three‐generation cohort. Concentrations of nine plasma cytokines (IFN‐γ, IL‐1β, IL‐4, IL‐6, IL‐10, IL‐12p40, IL‐12p70, IL‐13, and TNF‐α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. Results: Cross‐sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL‐4 levels during pregnancy and after delivery than the control group, and that plasma IL‐4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL‐10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL‐10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN‐γ, IL‐6, IL‐12p40, and TNF‐α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. Conclusions: These results suggest a potential protective effect of the anti‐inflammatory cytokines IL‐4 and IL‐10 during pregnancy against the development of PPD. [ABSTRACT FROM AUTHOR]

Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory and anti‐inflammatory properties may cause the biological activities of crocetin. Nevertheless, it is not still clear how this compound acts and causes an immune‐modulatory impact on human lymphocytes. The effects of three concentrations (5, 10, and 20 μM) of crocetin or dexamethasone (0.1 mM) were assessed on gene expression and secretion of cytokines, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) level, and nitric oxide (NO) production in phytohaemagglutinin (PHA)‐stimulated and non‐stimulated lymphocytes. By incubation with PHA, gene expression and cytokine concentration comprising interferon (IFN)‐γ, interleukin (IL)‐17A, IL‐10, and IL‐4 were increased, along with NF‐κB concentration and NO production (all, p < 0.001). In comparison with the controls, an alteration occurred in the T‐helper (Th)2/Th1 and Th17/Treg balance in the stimulated lymphocyte toward a Th2 and Th17 response. In stimulated cells, crocetin and dexamethasone decreased pro‐inflammatory significantly and increased anti‐inflammatory cytokines and related gene expression, respectively. Moreover, Th17/Treg and Th1/Th2 balance was changed toward Treg and Th1 significantly reducing NF‐κB and NO levels (p < 0.05 to p < 0.001). Promoting effects were represented by crocetin on T‐cell subsets to Treg and Th1. Hence, it can have therapeutic value for treating predominant diseases of Th2 or Th17 cells. [ABSTRACT FROM AUTHOR]

Background: While most studies focus on pro‐allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is not well elucidated. This study was to explore a novel anti‐inflammatory role and cellular/molecular mechanism of IL‐27 in allergic inflammation. Methods: A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, C57BL/6 or IL‐27Rα‐deficient (WSX‐1−/−) mice by short ragweed pollen, with untreated or PBS‐treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes (CLNs) were used for study. Gene expression was determined by RT‐qPCR, and protein production and activation were evaluated by immunostaining, ELISA and Western blotting. Results: Typical allergic manifestations and stimulated thymic stromal lymphopoietin (TSLP) signaling and Th2 responses were observed in ocular surface of EAC models in BALB/c and C57BL/6 mice. The decrease of IL‐27 at mRNA (IL‐27/EBI3) and protein levels were detected in serum, conjunctiva and CLN, as evaluated by RT‐qPCR, immunofluorescent staining, ELISA and Western blotting. EAC induced in WSX‐1−/− mice showed aggravated allergic signs with higher TSLP‐driven Th2‐dominant inflammation, accompanied by stimulated Th17 responses, including IL‐17A, IL‐17F, and transcription factor RORγt. In contrast, Th1 cytokine IFNγ and Treg marker IL‐10, with their respective transcription factors T‐bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)‐STAT1 and stimulated P‐STAT6 were revealed in EAC, especially WSX‐1−/−‐EAC mice. Conclusion: These findings demonstrated a natural protective mechanism by IL‐27, of which signaling deficiency develops a Th17‐type hyperresponse that further aggravates Th2‐dominant allergic inflammation. [ABSTRACT FROM AUTHOR]

White adipose tissue inflammation is linked with increased aromatase gene expression and estrogen production, a major risk factor for breast cancer in obese postmenopausal women. TNF-α, a proinflammatory cytokine, is a key driver of aromatase promoter I.4-mediated expression in adipose tissue. In this study, we have shown that IL-10, an anti-inflammatory cytokine, suppressed both TNF-α-stimulated human aromatase reporter-luciferase (hARO-Luc) expression in mouse bone marrow mesenchymal stromal cells and aromatase gene expression in human breast adipose stromal cells (ASCs). IL-10 blocked TNF-α-stimulated ERK1/2 activation in ASCs, suggesting an inhibitory effect through the MAPK signaling pathway. The links among obesity, IL-10, and aromatase were confirmed in ovariectomized (OVX) hARO-Luc mice, where increased adiposity was associated with upregulation of aromatase reporter activity and reduced IL-10 level in the mammary fat pad. OVX mice also exhibited changes in gut microbiota, similar to that in obese women, indicating altered immune function. In summary, our results suggest that increased adiposity, induced by the lack of ovarian hormones, results in enhanced expression of aromatase in mammary adipose tissue, mediated by reduction in local IL-10. These findings may bring new insights into the mechanisms involved in the development of postmenopausal breast cancer, as well as novel approaches for prevention. [ABSTRACT FROM AUTHOR]

1. The role of cytokines in cardiovascular control, especially in neurogenic hypertension, has received considerable attention during the past few years. Brain cytokines have been shown to exert profound effects on neuronal activity. Recently, a number of studies have shown that administration of pro-inflammatory cytokines or anti-inflammatory cytokines into the central nervous system has a significant impact on sympathetic outflow, arterial pressure and cardiac remodelling in experimental models of hypertension and heart failure. 2. Our objective in this review is to present a succinct account of the effect of cytokines on neuronal activity and their role in cardiovascular disease. Furthermore, we propose a hypothesis for a neuromodulatory role of cytokines in the neural control of cardiovascular function. [ABSTRACT FROM AUTHOR]

Background and Objectives: Interleukin-4 (IL-4), secreted mainly by T-helper 2 cells, is a key cytokine for the growth and proliferation of B lymphocytes. Previous studies have proved that IL-4 has an anti-inflammatory effect owing to its efficient inhibition of the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α), IL-1α, IL-1β, IL-6 and IL-8 by monocytes/macrophages. The aim of the present study was to assess the relation between clinical parameters and concentrations of IL-4 within gingival crevicular fluid from inflamed gingiva and periodontitis sites and, subsequently, after treatment of the periodontitis sites. Material and Methods: A total of 60 subjects were divided into three groups based on gingival index (GI), pocket probing depth and clinical attachment loss (CAL): healthy (group 1), gingivitis (group 2) and chronic periodontitis (group 3). A fourth group (group 4) consisted of 20 subjects from group 3, 6–8 weeks after treatment (i.e. scaling and root planing). Gingival crevicular fluid samples collected from each patient were quantified for IL-4 using the enzymatic immunometric assay. Results: The highest mean concentration of IL-4 was obtained for group 1 (99.39 ± 49.33 pg/mL) and the lowest mean concentration of IL-4 was obtained for group 3 (15.78 ± 21.92 pg/mL). The mean IL-4 concentrations for group 2 (64.34 ± 39.56 pg/mL) and group 4 (68.92 ± 42.85 pg/mL) were intermediate between the levels in healthy subjects and periodontitis subjects. Conclusion: The mean concentration of IL-4 decreased from periodontal health to disease. Thus, we suggest that type 2 helper T cell cytokine, as represented by IL-4, was associated with the remission or improvement of periodontal disease. [ABSTRACT FROM AUTHOR]

Neutrophils are the predominant inflammatory cells found in the vaginal discharge of patients with a Trichomonas vaginalis infection. Neutrophils have a shorter life span than other leucocytes. Our previous study indicated that live T. vaginalis alters Mcl-1 expression and caspase-3 activation, thereby inducing apoptosis of human neutrophils. However, it was previously unknown that the apoptotic neutrophils brought about by T. vaginalis can influence vaginal inflammation. Thus, human monocyte-derived macrophages (HMDM) were incubated with T. vaginalis -induced apoptotic neutrophils. Cytokine production and phagocytosis by HMDM were evaluated by ELISA and myeloperoxidase stain, respectively. HMDM showed increased anti-inflammatory cytokine production (IL-10) and decreased levels of pro-inflammatory cytokines, such as TNF-α and IL-6, compared with macrophages alone. Therefore, these results suggest that apoptotic neutrophils caused by T. vaginalis may lead to the resolution of vaginal inflammation by anti-inflammatory cytokine production in the human macrophages. [ABSTRACT FROM AUTHOR]

Background: Anti-inflammatory cytokines play an important role in downregulation of inflammation and the prevention of neoplastic disorders. Genetic variations of anti-inflammatory cytokines are assumed to influence such responses. The aim of the present study was to clarify the association between the IL-10 polymorphism, one of the representative anti-inflammatory cytokines, and susceptibility to gastric cancer and peptic ulcer in Japan. Methods: The IL-10-1082 (A/G)/-819 (T/C)/-592 (A/C) polymorphisms were assessed in Helicobacter pylori-positive patients with gastritis only ( n = 162), gastric ulcers ( n = 110), duodenal ulcers ( n = 94), or gastric cancers ( n = 105), and H. pylori-negative controls ( n = 168) by allele specific primer–polymerase chain reaction methods. Results: The carriage of IL-10-592 C (age and sex-adjusted odds ratio [OR]: 1.851, 95% confidence interval [CI]: 1.018–3.380) and IL-10-819 C (adjusted OR: 1.868, 95%CI: 1.023–3.411) allele were associated with an increased risk for gastric cancer development, not gastric ulcer and duodenal ulcer. The IL-10-1082 polymorphism had no association with development of gastric cancer and peptic ulcers. The presence of the ATA/GCC haplotype of IL-10-1082/-819/-592 polymorphism significantly increased the risk of gastric cancer development (adjusted OR: 2.805, 95%CI: 1.258–6.254) compared with presence of the ATA/ATA haplotype. Conclusions: The IL-10-1082/-819/-592 genotype status and haplotype were associated with an increased risk for gastric cancer development, not peptic ulcer, in Japan. The genotyping test of this anti-inflammatory cytokine would be useful for the detection of individuals with higher risk of gastric cancer development. [ABSTRACT FROM AUTHOR]