Prevention of arthritis by interleukin 10-producing B cells

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-{gamma}. Transfer of these B cells into DBA/1-TcR-ß-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti–IL-10/anti–IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders

Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus

Differences in Inflammatory Markers between Nulliparous Women Admitted to Hospitals in Preactive vs Active Labor

Objective To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. Study Design Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1β, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. Results Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P \u3c .001 and P = .003, respectively). Conclusion Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission

Hubungan Peningkatan Interleukin-10 Akibat Infestasi Cacing Usus Nematoda terhadap Spektrum Morbus Hansen

Morbus Hansen (MH) adalah infeksi kronis yang disebabkan oleh Mycobacterium leprae, yang mengenai saraf perifer, kulit, dan organ lain kecuali susunan saraf pusat. Pertahanan terhadap M. leprae tergantung pada respon imun efektif T helper tipe 1 (Th1), di sisi lain, peningkatan Interleukin-10 (IL-10) yang dihasilkan oleh Th2 dikenal sebagai mediator penting dalam pertahanan host terhadap infestasi cacing usus . Tujuan penelitian ini untuk menginvestigasi hubungan peningkatan IL-10 akibat infestasi cacing usus nematoda dengan spektrum Morbus Hansen. Penelitian observasional analitik laboratorik dengan rancangan potong lintang dilakukan dari Desember 2014 sampai Februari 2015 di Departemen Kulit dan Kelamin Rumah Sakit Umum Dr. Mohammad Hoesin Palembang dan Rumah Sakit Kusta Dr Rivai Abdullah. Total 158 pasien MH dilakukan untuk pemeriksaan feses dan kadar IL-10 dengan menggunakan teknik sandwich enzym immunoassay kuantitatif. Hasil penelitian menunjukkan hubungan yang signifikan antara durasi pengobatan dan MH spektrum dengan p = 0,002 (p <0,05), infestasi cacing usus dan spektrum MH dengan p = 0,000 (Odds Ratio 52,8; interval kepercayaan 95%: 7018 - 398714) , kadar IL-10 dan infestasi cacing usus dengan p = 0,000000002, kadar IL-10 dan spektrum MH dengan p = 0,0005. Peneliti melaporkan hubungan yang signifikan antara infestasi cacing usus dengan MH bentuk multibasiler (p = 0,000). Hasil penelitian kami menunjukkan infestasi cacing usus yang telah ada sebelumnya dapat memfasilitasi terjadinya infeksi Mycobacterium leprae atau perkembangan bentuk MH yang lebih berat. Penelitian ini menunjukkan infestasi cacing usus merupakan faktor risiko MH multibasiler

Immunomodulation by Interleukin-10 Therapy Decreases the Incidence of Relapse and Prolongs the Relapse-free Interval in Psoriasis

The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 µg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan–Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 ± 12.6 d in the interleukin-10 group in comparison with 66.4 ± 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile

The Effects Of 5-Ht4 Receptor Agonists On Interleukin-10 Knockout Mice

Recent studies have demonstrated that activation of the 5-HT4 receptors in the colonic mucosa can have healing and protective actions in experimental models of colitis. These actions include increased mucus secretion, increased epithelial proliferation, and enhanced epithelial migration. Since these studies involved chemically induced models of colitis, the current investigation was conducted to test whether a protective action of 5-HT4 receptor stimulation could be detected in Interleukin-10 knockout (IL-10 KO), which develop colitis spontaneously due to the absence of the anti-inflammatory cytokine, interleukin-10. Upon weaning, the IL-10 knockout mice were separated into two groups: an agonist group and a vehicle control group. The agonist group received 1 mg/kg tegaserod in a vehicle consisting of 0.9% saline each day by enema of dimethyl sulfoxide (DMSO) in saline each day, while the control group received daily enemas of vehicle over the course of 21 days. Several outcome measures were used to assess the effectiveness of the treatment. To evaluate the severity of colitis, disease activity index was monitored, and histologic damage was blindly scored. Administration of tegaserod by enema to the IL-10 KO mice had a significant protective effect on the treated mice. The disease activity index (DAI) of agonist treated mice was significantly better than that of vehicle treated mice over time (p\u3c0.001; 2-way ANOVA). Mice treated with vehicle had a more significant decline in health over time versus the agonists, with more blood present in feces and a looser/diarrhea-like consistency in stool. The histological damage score (HDS) was also improved by 5-HT4 agonist treatment (p\u3c0.05, t-test). Sections of vehicle treated colons showed significantly greater damage, including epithelial erosions, the presence of polymorphonuclear cells, and abnormal crypt architecture (cryptitis), than those treated with the 5-HT4 receptor agonist tegaserod. During the 21-day course of the current investigation, there was no difference in the survival data between the two groups. These data, when taken together, suggest that administration of the 5-HT4 receptor agonist tegaserod via enema to IL-10 KO mice has a greater healing and protective effect than seen in the IL-10 KO mice that received vehicle. We proposed to test the hypothesis that treatment of IL-10 knockout colitis with a 5-HT4 receptor agonist will attenuate the development of colitis and have healing and protective effects in the colons of the treated mice

Interleukin-10 Promoter Polymorphisms and Susceptibility to Skin Squamous Cell Carcinoma After Renal Transplantation

After organ transplantation, susceptibility to cancer is multifactorial, especially for skin carcinomas. Risk factors may include genetic susceptibilities, such as the control of cytokine production. Interleukin-10 is a cytokine that is implicated in tumorigenesis, and it has been shown that polymorphisms in its gene promoter correlate with differential amounts of production. The aim of this study was to investigate a possible association between interleukin-10 gene promoter polymorphisms and the occurrence of skin carcinomas after renal transplantation. Seventy kidney transplant recipients who developed a squamous cell carcinoma or a basal cell carcinoma were examined for polymorphisms in the interleukin-10 gene promoter using polymerase chain reaction based methods. Single base pair mutations were studied at positions –1082, –819, and –592. These patients were compared to 70 healthy controls and to 70 matched renal transplant recipients without cancer. The interleukin-10 secretion capability was tested in a subgroup of 40 of these patients by in vitro stimulation of peripheral mononuclear cells. Interleukin-10 genotypes and haplotypes were differently distributed in kidney transplant recipients who developed a skin carcinoma, but especially a squamous cell carcinoma, with an increased frequency of the GCC haplotype and a decreased frequency of the ATA haplotype. Subsequently, we found a shift in the predicted phenotypes from the low production phenotype to the high production phenotype. Secretion of interleukin-10 was strongly correlated to the production predicted phenotype, and tended to be higher in patients who developed a squamous cell carcinoma than in the others. These results indicate that interleukin-10 gene polymorphisms and interleukin-10 production capability may contribute to the development of skin squamous cell carcinomas after renal transplantation

Association of interleukin 10 rs1800896 polymorphism with susceptibility to breast cancer: a meta-analysis.

Objective: To evaluate the correlation between interleukin 10 (IL-10) -1082A/G polymorphism (rs1800896) and breast cancers by performing a meta-analysis. Methods: The Embase and Medline databases were searched through 1 September 2018 to identify qualified articles. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were applied to evaluate associations. Results: In total, 14 case-control studies, including 5320 cases and 5727 controls, were analyzed. We detected significant associations between the IL10 -1082 G/G genotype and risk of breast cancer (AA + AG vs. GG: OR = 0.88, 95% CI = 0.80-0.97). Subgroup analyses confirmed a significant association in Caucasian populations (OR = 0.89, 95% CI = 0.80-0.99), in population-based case-control studies (OR = 0.87, 95% CI = 0.78-0.96), and in studies with ≥500 subjects (OR = 0.88, 95% CI = 0.79-0.99) under the recessive model (AA + AG vs. GG). No associations were found in Asian populations. Conclusions: The IL10 -1082A/G polymorphism is associated with an increased risk of breast cancer. The association between IL10 -1082 G/G genotype and increased risk of breast cancer is more significant in Caucasians, in population-based studies, and in larger studies

Expression of Interleukin-10 in Intestinal Lymphocytes Detected by an Interleukin-10 Reporter Knockin tiger Mouse

SummaryTo identify interleukin-10 (IL-10)-producing cells in vivo, we generated a knockin mouse where an internal ribosome entry site (IRES) green fluorescence protein (GFP) element was inserted immediately before the polyadenylation site of the IL-10 gene. GFP fluorescence in cells from these mice was found to correlate positively with IL-10 protein expression. With this model, we found that after multiple T cell receptor (TCR) stimulations, strong expression of IL-10 was produced specifically by intraepithelial lymphocytes (IEL) in the small intestine and colonic lamina propria lymphocytes (cLPL). We found that anti-CD3 treatment induces T regulatory cell 1 (Tr1)-like cells in small intestinal IEL (sIEL) and led to the accumulation of naturally occurring regulatory T (nTreg) cells in colonic LPL (cLPL). These findings highlight the intestine as a unique site for induction of IL-10-producing T cells, which play a critical role in the regulation of inflammation in the gut