Iranian journal of immunology
Volume:15 Issue: 3, Summer 2018

Interleukin-1 family 7 (IL-1F7) is a novel member of IL-1F cytokines. IL-1F7 is more commonly known as IL-37. IL-37 join the α-subunit of the IL-18 receptor, or IL-18 binding protein (IL-18BP), and binding of these proteins can enhance the IL-18 suppression. IL-37 also translocates to the cell nucleus and affects gene transcription. IL-37 inhibits the phosphorylation of p38 mitogen-activated protein kinases. Almost all reports showed that IL-37 has remarkable anti-inflammatory activity. IL-37 plays an important role in a variety of inflammatory and autoimmune diseases, as well. Recently, studies demonstrated that the expression of IL-37 is abnormal in many diseases such as inflammatory bowel diseases, inflammatory respiratory diseases, atherosclerosis, hepatitis, obesity, contact hypersensitivity, Graves’ disease, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Behcet's disease. Here, we will review the biological characteristics of IL-37 and its key roles in various inflammatory and autoimmune diseases.

Polycystic ovary syndrome (PCOS) is considered as the most common cause of female infertility that affects 4-10% of women in the reproductive age. Previous studies have shown the role of a balanced immune response in a successful pregnancy and fertility. To investigate the T helper cells type 1 (Th1) /Th2/Th17/Treg paradigms in peripheral blood of infertile PCOS compared with normal fertile women. Peripheral blood mononuclear cells (PBMCs) were isolated at the late follicular phase from 10 PCOS and 10 fertile women. PBMCs were stimulated with PMA and ionomycin in the presence of Berefeldin A as Golgi stop agent to detect intracellular cytokine production (IFN-γ, IL-17, and IL-4) from CD3+CD4+T cells population indicating T helper (Th) cells subsets by flowcytometry. Moreover, regulatory T cells were enumerated using CD25 and Foxp3 markers. In this study, we report that the frequency of Th1 cells was increased compared to Th2 cells in infertile PCOS when considering Th1/Th2 ratio (P=0.05). Analysis of Th17/Th2 ratio showed a significant difference with a bias toward Th17 dominancy in PCOS (P=0.02). The proportion of CD4+CD25+Foxp3+ regulatory T cells was significantly lower in PCOS patients than that of healthy fertile women (P=0.02). In summary, Th1 and Th17 bias and reduction of Treg and Th2 cells as regulators of immune responses might be involved in the pathogenesis of PCOS. These results are suggestive of an altered immune response to inflammatory status in PCOS patients, likely causing some complications such as infertility in these patien

Given the variations in clinical presentation and physiopathological mechanisms in irritable bowel syndrome (IBS) subtypes, it is an acknowledged fact that the response to treatments can be disparate. To assess the effect of vitamin D on inflammatory cytokines (IL-17, IL-10, TNF-α), and biomarkers of oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) among IBS patients. A double-blind, randomized, placebo-controlled 6-month intervention study was carried out on 90 IBS patients (85 were analyzed), as defined by the Rome III criteria. Study participants were randomly assigned to receive either 50,000 IU vitamin D3 or a placebo fortnightly. Vitamin D supplementation significantly reduced the IL-17 and MDA serum levels (P<0.05) and observably increased the TAC and IL-10 serum levels (P<0.05), compared with the placebo group. Comparing different bowel habit subtypes, we observed that it was only in diarrhea predominant IBS (IBS-D) that vitamin D supplementation was able to significantly reduce the serum levels of TNF-α and IL-17 (P<0.05). However, in all subtypes, IL-10 and TAC increased, while MDA decreased (P<0.05) in vitamin D group, compared to the placebo group. Vitamin D3 supplementation reduces the serum IL-17 and MDA levels, and augments the serum IL-10 and TAC levels in IBS patients, particularly in IBS-D subtype. Thus, the present study demonstrates the beneficial effects of vitamin D on patients with IBS-D

Human leukocyte antigen (HLA) complex is a gene family involved in antigen presentation associated with protection or susceptibility to inflammatory, infectious and autoimmune diseases. Atherosclerosis is a chronic inflammatory disease in which HLA molecules play a role in the initiation and development of the disease through presentation of self or foreign antigens to T cells. To investigate the association of HLA-DRB1 alleles with atherosclerosis in a sample of southwestern Iranians. We performed an analytical cross-sectional study involving 96 patients with atherosclerosis and 72 controls. HLA-DRB1 genotyping was performed by PCR-SSP method. We observed a significantly lower frequency of DRB1*01 in patients with coronary artery atherosclerosis than in controls (4.68% vs. 13.1, P=0.0052, OR=3.09, CI 95%: 1.35-7.05). However, this allele showed a positive association with high blood pressure (P=0.009) in patients. Furthermore, DRB1*16 allele was associated with hyperlipidemia (P=0.008) in patients. Our results demonstrated that DRB1*01 may be a protective allele against atherosclerosis in individuals who live in southwest of Iran. The mechanism of this protection needs further investigation

Cholera disease caused by Vibrio cholerae remains a major cause of morbidity and mortality throughout the world. Various strategies with different proteins as immunogens have been tried for vaccine development, none of which have been sufficiently effective to preclude cholera. Chimeric proteins, with their ability to present multiple antigens at the same time, can play important roles in immunization. To evaluate the immunogenicity of a chimeric construct, comprised of OmpW and CtxB as immunogenic proteins of Vibrio cholera, in BALB/c mice. The construct was designed after bioinformatics assessments and then expressed in E.coli. Chimeric protein, OmpW, and CtxB were purified with Ni-NTA chromatography and confirmed by Western blotting. Mice were immunized with purified recombinant proteins. The antibody titers and specificity of the immune sera were then analyzed by ELISA and challenged on the pups of immunized mice with 1, 5 and 10 LD50. Mice ileal loop assay was also performed. Significant differences were observed in antibody titers in immunized mice compared to the control groups. Infant mouse challenge was performed so as to compare the protective efficacies of the selected immunogen regimens. Of the Pups from dams immunized with chimeric protein which received 1 LD50, 75% survived. Pups belonging to PBS-immunized dams, experienced 100% mortality. The serum raised toward immunogenic construct, inhibited cholera toxin activity in ileal loop test up to 68%. Chimeric construct is able to induce the immune system and provide up to 75% inhibition of toxin activity against 1 LD50 of Vibrio cholerae.

Cerebral sinovenous thrombosis (CSVT) is a neurovascular disorder that occurs when a blood clot develops in a vein near the brain. Evaluating the subsequent changes in inflammatory cytokines can better reveal the underlying pathogeneses.

To assess the serum levels of interleukin-10 (an anti-inflammatory cytokine) and IL-17 (a pro-inflammatory cytokine) in patients with aseptic non-vasculitic CSVT.

In this prospective case-control study, 31 patients with aseptic non-vasculitic CSVT (admitted in Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran) were enrolled. IL-10 and IL-17 serum levels were measured at diagnosis, before initiation of treatment (acute stage), 3 months later (subacute stage). These cytokines were also measured in samples obtained from 30 gender- and age-matched healthy subjects, which were considered as control values.

Patients’ IL-10 and IL-17 levels were higher in both acute and subacute stages as compared to controls. However, no significant differences existed between the acute stage and control groups for both cytokines. Moreover, subacute levels were significantly higher than their acute and control levels.

This study demonstrated the alteration of IL-10 and IL-17 levels in aseptic non-vasculitic CSVT. The rise in subacute IL-10 can be explained by the assumption that IL-10 is released as an anti-inflammatory response to subside the effects of IL-17 mediated reactions. More importantly, the immediate sampling in the acute stage did not allow enough time for triggering the immune system to produce such mediators. However, a balance was established between IL-10 and IL-17 in the subacute stage to prevent

Alginate materials have been widely employed for biomedical applications ranging from wound healing to cancer treatment. However, how alginate materials affect the immune system is largely unknown. To explore the impact of alginate materials on immune system. The effect of three types of alginate materials, low viscosity, high viscosity and particulate alginate, were examined by both in vivo and in vitro analyses. C57BL/6J (B6) mice were treated with alginate and peripheral blood was tested by ELISA for cytokine production. Dendritic cells, macrophages and splenocytes isolated from mice were analyzed for the response to alginate treatment. Administration of alginates by intra lymph node injection (I.L.N.) yielded more potent cytokines productions than other injection routes. Alginate materials did not affect the viability of lymphocytes. Particulate alginate induced the most potent inflammatory reaction as determined by the production of cytokines, such as, IL-1β, IL-8, TNF-α and IFN-γ. Low viscosity and particulate alginates are more effective than high viscosity alginates in activating dendritic cells as indicated by the expression of dendritic cells surface markers (CD80, CD86 and CD40). Similarly, the level of G-CSF was slightly higher in particulate alginate treated macrophages. Alginate materials could affect immune response through different ways, including promoting inflammatory cytokine production, and activating dendritic cells. Therefore, alginate materials, especially in particulate form, have the potential to be applied in inflammation related diseases.

CD163-expressing macrophages are involved in the inflammatory response in asthma. To assess sputum and serum soluble CD163 (sCD163) and cytokine levels in patients with asthma. Further discussed was the difference between sCD163 and other classic inflammatory mediators. Sputum was successfully induced in asthma patients (n=85) and healthy controls (n=21). Interleukin (IL)-4, IL-5, IL-1β, IL-8, IL-9, IL-6, and sCD163 levels in sputum were measured. CD163+ monocytes in blood were evaluated using flow cytometry. Sputum sCD163 level significantly increased in asthma (median: 22.4 pg/ml; IQR, 11.52-42.91), unlike healthy controls (10.54 pg/ml;9.85-23.5; P<0.001). Sputum sCD163 (P=0.020) and serum sCD163 (P=0.032) levels were significantly higher in patients with severe asthma compared to those with mild/moderate asthma. Percentage of CD163+ monocytes in patients with asthma was significantly lower than the controls (P<0.001). Increased sCD163 levels in sputum are associated with the impairment of lung function.