Concentrations Of Interleukin-22 Research Articles

Interleukin-22/Interleukin-22 binding protein axis and oral contraceptive use in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with alterations in gut microbiota. The cytokine interleukin-22 (IL-22) is produced by immune cells and closely linked to gut immunity, which is tightly controlled by its binding protein (IL-22BP). In this study, we aimed to assess whether IL-22/IL-22BP axis is altered in PCOS at baseline and in response to short-term oral contraceptive (OC) therapy. We have evaluated circulating concentrations of IL-22 and IL-22BP in serum samples of 63 PCOS patients and 39 age- and BMI-matched healthy controls. Blood samples were taken in the early follicular phase of a cycle and stored at -80 °C. Serum IL-22 and IL-22BP levels were measured by ELISA at baseline in both women with PCOS and controls, and after 3 months of OC use in PCOS group. IL-22/IL-22BP ratio was calculated in order to have a better reflection of IL-22 biological activity. At baseline, serum IL-22, IL-22BP concentrations and IL22/IL-22BP ratio were similar between women with PCOS and healthy controls. Three months of OC use along with general lifestyle advice resulted in a significant increase in IL-22/IL-22BP ratio in the PCOS group (62.4 [IQR:14.7-172.7] at baseline vs 73.8 [IQR:15.1-264.3] after OC use respectively p = 0.011). Results of this study show that women with PCOS have similar circulating concentrations of IL-22 and IL-22BP with healthy women and that short term oral contraception is associated with an increase in IL-22/IL-22BP ratio suggesting higher biological activity of the IL-22 system with OC use in PCOS.

An elevated deoxycholic acid level induced by high-fat feeding damages intestinal stem cells by reducing the ileal IL-22

Long-term high-fat diet (HFD) destroys the intestinal mucosal barrier by damaging intestinal stem cells (ISCs). A HFD can increase the concentration of intestinal deoxycholic acid (DCA) and decrease the secretion of interleukin-22 (IL-22), which plays an important role in the proliferation, repair and regeneration of ISCs. We hypothesized that increased level of intestinal DCA induced by a HFD leads to ISC dysfunction by reducing the IL-22 levels in intestinal tissues.In this study, 2 weeks of a DCA diet or a HFD damaged ileal ISC and its proliferation and differentiation, resulting in a decrease in Paneth cells and goblet cells. Importantly, 2 weeks of a DCA diet or a HFD also reduced ileal IL-22 concentration, accompanied by a decreased number of group 3 innate lymphoid cells in ileal mucosa, which produce IL-22 after intestinal injury. Concurrent feeding with bile acid binder cholestyramine prevented all these changes induced by a HFD. In addition, in vitro study further confirmed that exogenous IL-22 reversed the decline in the proliferation and differentiation of ileal ISCs induced by DCA stimulation. Collectively, these results revealed that the decrease in intestinal IL-22 induced by DCA may be a novel mechanism by which HFD damages ISCs. The administration of IL-22 or a bile acid binder may provide novel therapeutic targets for the metabolic syndrome caused by a HFD.

Expression of Serum IL-22, IL-23, and TLR9 as Tumor Markers in Untreated Breast Cancer Patients

Breast cancer (BC) is the most common cancer among women and is the most important cause of death among them. Breast cancer is a common malignancy, accounting for one-third of women cancers in Iraq. To the best of our knowledge, little literature information is available on the participation of Interleukin-22 (IL-22), interleukin-23 (IL-23), and Toll-like receptor 9 (TLR9) in BC patients. Thus, the evaluation of serum IL-22, IL-23, and TLR9 level changes can add new information on their roles in breast cancer development and progression. The present study aimed to evaluate the clinical usefulness of IL-22, IL-23, and TLR9 as tumor markers in BC. Levels of circulating interleukin-22, IL-23, and TLR9 were estimated by the enzyme-linked immunoassay method. The serum level of IL-22 was highly significantly elevated in patients compared to the benign and healthy control groups (317.53 ± 14.33 vs. 68.73 ± 12.38 and 62.67 ± 19.11 pg/mL, p ≤ 0.05), but the difference between the benign tumor and healthy control groups means was not significant. Also, these results indicated that the mean level of IL-23 was higher significantly in breast cancer patients in comparison with the benign and healthy controls (887.89 ± 199.04 vs. 146.86 ± 84.26 and 72.26 ± 12.76 pg/mL, p ≤ 0.05). So, no significant difference was revealed between a benign tumor and healthy control groups (146.86 ± 84.26 and 72.26 ± 12.76 pg/mL, p andgt; 0.05). Finally, a serum level of TLR9 was significantly elevated in breast cancer patients in comparison with the control groups (16.89 ± 0.75 vs. 9.97 ± 1.21 ng/mL, 9.06 ± 0.21 ng/mL, p less than 0.05). On estimating IL-22, IL-23, and TLR9, the results showed the concentrations of IL-22, IL-23, and TLR9 in the sera of breast cancer were significantly elevated as compared to those in the control groups. Expression of IL-22, IL-23, and TLR9 could be used as a diagnostic tumor biomarker.

Gingival crevicular fluid levels of Interleukin-22 (IL-22) and human β Defensin-2 (hBD-2) in periodontal health and disease : A correlative study

BackgroundInterleukin 22(IL-22), a recently identified, Th-22 associated cytokine has a key role in the production of human β defensin-2(hBD-2) and hence an indirect role in innate, nonspecific immunity. Hence this study was conducted as preliminary research to quantify and correlate the levels of IL-22 and hBD-2 in periodontal disease. Materials and methodsGingival crevicular fluid from subjects with chronic periodontitis (n = 27), gingivitis (n = 25) and healthy controls (n = 27) were obtained for the study. The periodontal status of each subject was assessed by criteria based on plaque index, gingival index, bleeding on probing, probing depth and clinical attachment loss. The levels of IL-22 and hBD-2 were measured in GCF samples with an enzyme-linked immunosorbent assay. ResultPeriodontal parameters were described and reported as mean values. The distribution and comparison of clinical parameters and gingival crevicular fluid IL-22, hBD-2 levels in healthy controls, gingivitis and chronic periodontitis groups were assessed using one way ANOVA test. Post Hoc Bonferroni test was used for intergroup comparisons. Association among the IL-22 , hBD-2 and clinical parameters in all three groups were examined using Pearson's correlation test.The IL-22 level was significantly greater in chronic periodontitis group than healthy controls (P < 0.001) and gingivitis group (P < 0.001). The hBD-2 level was significantly higher in the chronic periodontitis group compared to gingivitis (P = 0.003) and healthy controls (P < 0.001). The results also showed a statistically significant correlation (P = 0.002) between IL-22 and hBD-2 concentration in chronic periodontitis group. ConclusionThese results indicate the role of IL- 22 and hBD-2 in the innate immune response during periodontitis.

Changes in serum IL-22 level in patients with hypertensive renal damage and its clinical significance

To observe the changes in serum interleukin-22 (IL-22) level and its correlation with other clinical indexes in patients with essential hypertension and hypertensive renal damage, and to investigate its effects and clinical significance. Methods: A total of 97 essential hypertension (EH) patients and 40 healthy control were enrolled in this study. The EH patients were divided into a simple hypertension (SH) group (n=45) and a hypertensive renal damage (HRD) group (n=52) according to 24 h urinary protein (24 h-UPRO) level. Basic clinical data were collected; serum IL-22 level was detected by enzyme-linked immunosorbent assay (ELISA); the proportion of Th22 cells in peripheral blood was evaluated by flow cytometry (FCM); and serum high sensitivity C-reactive protein (hs-CRP) concentration was measured by immune turbidimetry. Correlation analysis was applied between serum IL-22 level and other indexes. Results: Serum IL-22 level and Th22 cell proportion in patients with hypertension were significantly higher than those in the healthy controls (all P<0.01). Compared with the SH group, serum IL-22 level and Th22 cell proportion were significantly elevated in the HRD group (P<0.01, P<0.05, respectively). Bivariate linear correlation analysis revealed that serum IL-22 level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hsCRP (r=0.367, P<0.01; r=0.402, P<0.01; r=0.329, P<0.05); there was also a positive correlation between serum IL-22 concentration and Th22 cell proportion (r=0.478, P<0.01) in the SH group. Serum IL-22 level was positively correlated with 24 h-UPRO level (r=0.318, P<0.05) in the HRD group. Conclusion: Serum IL-22 level and peripheral blood Th22 cells are significantly increased in the HRD group compared with the SH group. Serum IL-22 level is closely correlated with extent of hypertensive renal damage, indicating that serum IL-22 level may involve in the pathogenesis of hypertensive renal damage.

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population.

The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR)=2·24, 95% confidence interval (CI)=1·22-4·12, P=0·010; G versus· A: adjusted OR=2·18, 95% CI=1·20-3·97, P=0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR=3·09, 95% CI=1·30-7·33, P=0·011; AG versus· AA: aOR=3·25, 95% CI=1·35-7·85, P=0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P=0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22.

Effect of Differential Exercise Intensities on Interleukin-22 in Metabolic Syndrome

Elevated serum interleukin-22 (IL-22) concentration is independently associated with the incidence of type 2 diabetes and coronary artery disease. Individuals with metabolic syndrome (MetS) are at increased risk of developing both conditions.Paradoxically, evidence also exists demonstrating that IL-22 may have a role in the alleviation of MetS. PURPOSE: We investigated the impact of moderate-intensity continuous training (MICT) and different volumes of high-intensity interval training (HIIT) on IL-22. METHODS: This was a sub-study of the ‘Exercise in prevention of Metabolic Syndrome’ (EX-MET) multi-center randomized trial, based on data collected at the Brisbane site. Thirty-nine MetS individuals were randomized to one of three 16-wk interventions: i)MICT(n=10,30min at 60-70%HRpeak,5x/wk);ii)4HIIT(n=13, 4x4min at 85-95%HRpeak,interspersed with 3min of recovery at 50-70%HRpeak,3x/wk);or iii)1HIIT(n=16,1x4min at 85-95%HRpeak, 3x/wk).Serum IL-22 concentration was measured following a 12-hr fast via enzyme linked immunosorbent assays, before/after the intervention.MetS severity, cardiorespiratory fitness (CRF), insulin resistance(IR), and visceral adipose tissue(VAT) were also measured via MetS z-score,HOMA-IR,dual-energy x-ray absorptiometry, and indirect calorimetry, respectively. RESULTS: The median (IQR) IL-22 percent changes from pre- to post-intervention in the MICT, 4HIIT, and 1HIIT groups were -17%(-43.0%;31.3%),+16.5%(-18.9%;154.9%), and +15.9%(-28.7%;46.1%) respectively. Although there was no significant between-group difference in IL-22 change, there was a medium-to-large group x time interaction effect on this cytokine[F(2,35)=2.08, p=0.14,η2=0.14].There were similar reductions in MetS severity(MICT,-0.5±1.8; 4HIIT,-0.5±0.9;1HIIT,-1.3±1.8), IR(MICT,-2.1±2.7;4HIIT,-0.8±1.4;1HIIT,-1.0±2.0), and VAT(MICT,-47.2±152.6g; 4HIIT,-68.2±106.0g; 1HIIT,-44.9±102.7g) following all interventions. 4HIIT(+5.7±4.7ml/kg/min) significantly improved CRF more than MICT (+2.7±1.9ml/kg/min) and 1HIIT (+2.9±2.2ml/kg/min). CONCLUSION: Although there was no significant between-group difference in IL-22 change, the study suggests that different exercise intensities may have different effects on IL-22 in MetS individuals.

Effect of allogenic mesenchymal stem cells transplantation on the expression of interleukin-22 and matrix metalloproteinase-3 in rats with collagen induced arthritis

Objective: To study the effect of allogeneic bone marrow mesenchymal stem cells transplantation on the expression of interleukin -22 (IL-22), matrix metalloproteinase -3 (MMP-3) in serum and synovial of rats with collagen induced arthritis. Methods: Type Ⅱ collagen were injected twice to establish the collagen induced arthritis (CIA) rat model. Forty-eight rats were randomly divided into 3 groups: control group, CIA control group, CIA experiment group. Rat bone marrow mesenchymal stem cells were cultured by bone marrow method combined with adherent culture method. After identify, the remaining cells were injected in the CIA experimental group. Enzyme linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of IL-22 and MMP-3 in serum and anklebone joint's synovium of rats, respectively. Synovial cells were isolated and cultured, and were treated with different concentrations of IL-22. MMP-3 protein and mRNA were detected before and after stimulation by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results: After MSC transplantation, arthritis index, X-ray, HE staining of CIA rat showed that joint damage significantly reduced compared with the control group. The ELISA results showed that the expression of MMP-3 and IL-22 in CIA control group was higher than those in the control group (125.79±9.12 vs 102.00±7.63 ng/ml, P<0.05), (292.35±31.23 vs 257.27±13.99 ng/ml, P<0.05) and CIA experiment group (125.79±9.12 vs 97.94±9.50 ng/ml, P<0.05), (292.35±31.23 vs 262.16±22.02 ng/ml, P<0.05) with statistically significant difference (P<0.05). There was no significant difference between the control group and CIA experimental group. Immunohistochemical showed similar results with ELISA. Western blotting and RT-qPCR showed that MMP-3 protein and mRNA expression was increased after IL-22 stimulation in a dose-dependent manner. Conclusion: IL-22 and MMP-3 play an important role in the pathogenesis of rheumatoid arthritis. IL-22 could regulate the expression of MMP-3, and bone marrow mesenchymal stem cells could reduce the expression of MMP-3 in the treatment of rheumatoid arthritis by reducing the expression of IL-22.

Effect of interleukin-22 on proliferation and activation of hepatic stellate cells induced by acetaldehyde and related mechanism

Objective: To investigate the effect of interleukin-22 (IL-22) on the activation and proliferation of hepatic stellate cells (HSCs) induced by acetaldehyde, as well as the role of the antioxidant axis Nrf2-keap1-ARE. Methods: Hepatic stellate cell-T6 (HSC-T6) cells were cultured in vitro, and after 24 and 48 hours of acetaldehyde stimulation at various concentrations (25, 50, 100, 200, and 400 μmol/L), MTT assay was used to measure cell proliferation rate to screen out the optimal conditions for model establishment. HSC-T6 cells were treated first with the optimal concentration of acetaldehyde (200 μmol/L) for 24 hours and then with different concentrations of IL-22 (10, 20, and 50 ng/ml) for 24 hours. MTT assay was used to measure cell proliferation, Western blot and cell immunohistochemistry were used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and α-smooth muscle actin (α-SMA), and spectrophotometry was used to measure the changes in the content of malondialdehyde (MDA) and reduced glutathione (GSH) in culture supernatant. SPSS 17.0 was used for statistical analysis and data were expressed as mean±SD. P < 0.05 was considered statistically significant. A one-way analysis of variance was used for comparison of means between any two groups. Results: HSCs had significantly enhanced proliferation and activation after being treated with acetaldehyde, especially at 200 μmol/L for 48 hours. After the intervention with gradient concentrations of IL-22, the proliferation and activation of HSCs were inhibited in a dose-dependent manner, and the proliferation and migration rates in the 10, 20, and 50 ng/ml IL-22 groups were 14%, 25%, and 35%, respectively (all P < 0.05). The results of Western blot and immunohistochemistry showed that there was no significant difference in the expression of Nrf2 total protein in HSCs between groups, while there was extremely low expression of Nrf2 nucleoprotein in the blank control group. There was increased expression of Nrf2 nucleoprotein after acetaldehyde stimulation (compared with the blank control group, P < 0.05), and after the intervention with gradient concentrations of IL-22, the expression of Nrf2 nucleoprotein was further increased (all P < 0.05). The results of spectrophotometry showed that compared with the blank control group, the model group had increased levels of MDA and GSH in culture supernatant after acetaldehyde stimulation; after the intervention with gradient concentrations of IL-22, there was a significant reduction in the MDA level and a significant increase in the GSH level in a dose-dependent manner (all P < 0.05). Conclusion: The activation and proliferation of HSCs induced by acetaldehyde helps with the successful establishment of an in vitro model of alcoholic liver fibrosis. IL-22 effectively inhibits the activation and proliferation of HSCs induced by acetaldehyde, and its mechanism may be related to promoting Nrf2 nuclear translocation in HSCs and expression of the downstream target gene GSH and increasing the activity of the antioxidant axis Nrf2-keap1-ARE.

Interleukin-22 is elevated in lavage from patients with lung cancer and other pulmonary diseases.

BackgroundInterleukin-22 (IL-22) is involved in lung diseases such as pneumonia, asthma and lung cancer. Lavage mirrors the local environment, and may provide insights into the presence and role of IL-22 in patients.MethodsBronchoscopic lavage (BL) samples (n = 195, including bronchoalveolar lavage and bronchial washings) were analysed for IL-22 using an enzyme-linked immunosorbent assay. Clinical characteristics and parameters from lavage and serum were correlated with lavage IL-22 concentrations.ResultsIL-22 was higher in lavage from patients with lung disease than in controls (38.0 vs 15.3 pg/ml, p < 0.001). Patients with pneumonia and lung cancer had the highest concentrations (48.9 and 33.0 pg/ml, p = 0.009 and p < 0.001, respectively). IL-22 concentration did not correlate with systemic inflammation. IL-22 concentrations did not relate to any of the analysed cell types in BL indicating a potential mixed contribution of different cell populations to IL-22 production.ConclusionsLavage IL-22 concentrations are high in patients with lung cancer but do not correlate with systemic inflammation, thus suggesting that lavage IL-22 may be related to the underlying malignancy. Our results suggest that lavage may represent a distinct compartment where the role of IL-22 in thoracic malignancies can be studied.

Clinical Implications of Hepatocyte Growth Factor, Interleukin-20, and Interleukin-22 in Serum and Bronchoalveolar Fluid of Patients with Non-Small Cell Lung Cancer.

Hepatocyte growth factor (HGF) is involved in tumorigenesis, interleukin-20 (IL-20) is an inhibitor of angiogenesis, and interleukin-22 (IL-22) stimulates tumor growth. The aim of this study was to determine the level of HGF, IL-20, and IL-22 in both serum and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients before onset of chemotherapy, the nature of the interrelationships between these markers, and their prognostic significance regarding post-chemotherapy survival time. We studied 46 NSCLC patients and 15 healthy subjects as a control group. We found significantly higher serum levels of HGF and IL-22 in the NSCLC patients than those in controls [pg/ml: HGF - 1911 (693-6510) vs. 1333 (838-3667), p = 0.0004; IL-22 - 10.66 (1.44-70.34) vs. 4.69 (0.35-12.29), p = 0.0007]. In contrast, concentrations of HGF and IL-22 in BALF were lower in NSCLC patients than those in controls [pg/ml: HGF - 72 (6-561) vs. 488 (14-2003), p = 0.0002; IL-22 - 2.28 (0.70-6.52) vs. 3.72 (2.76-5.64), p = 0.002]. In the NSCLC patients, there was a negative correlation between the serum level of IL-20 and time to tumor progression (r = -0.405, p = 0.04) and between the serum level of HGF and survival time (r = -0.41, p = 0.005). In addition, a higher serum level of HGF and a higher BALF level of IL-22 in patients were linked with a shorter overall survival. We conclude that HGF, IL-20, and IL-22 in the serum and BALF of NSCLC patients before chemotherapy may be a prognostic of cancer progression.

Aberrant Expression of IL-22 Receptor 1 and IL-22 Stimulation Increase the Activation of STAT3 and ERK1/2 in ABC-DLBCL Cells

BACKGROUND: Interleukin-22 (IL-22) was recently discovered as a T-cell derived cytokine that belongs to the IL-10 gene family. It has been shown that IL-22 can promote cell proliferation and activate several oncogenic pathways including STAT3, MAPK and AKT signaling. IL-22 exerts its function by binding to its heterodimeric receptor complex which is composed of IL-22 receptor (R) 1 and IL-10R2. IL-22R1 is restricted and barely detected in normal immune cells including B and T cells. In the current study, we sought to determine whether IL-22 plays a part in the development of diffuse large B-cell lymphoma (DLBCL).METHODS: Plasma IL-22 level was measured in newly diagnosed patients with DLBCL and normal individuals by ELISA assay. We also assessed the expression of IL-22R1 in FFPE sample and DLBCL cell lines (TMD8, OCI-LY3, SUDHL16, OCI-LY1) by immunohistochemistry and immunofluorescence staining respectively. Immunoblotting was performed to determine changes of signaling pathways in cell lines upon the treatment with IL-22 recombinant protein.RESULTS: The plasma IL-22 concentration was significantly increased in newly diagnosed DLBCL patients (n=12) compared with normal individuals (n=26, P= 0.0177). IL-22R1 protein was expressed in all of the four DLBCL cell lines, while not all but some of the primary tumor samples expressed it on membranes of tumor cells. Using immunoblotting, we demonstrated a substantial increase of pSTAT3 level with the treatment of IL-22 in ABC-DLBCL cell lines TMD8 and OCI-LY3, while no pSTAT3 was detectable in GCB-DLBCL cell lines SUDHL16 and OCI-LY1. Interestingly, upon IL-22 stimulation, the p-ERK1/2 level was increased shortly and quickly returned to the normal level in TMD8 cells, and steadily increased in LY3 cells during 30 min of treatment. However, there was no change about p-ERK1/2 in SUDHL16 and OCI-LY1 cells after IL-22 treatment.CONCLUSIONS: Our current study has shown the aberrant expression of IL-22R1 in DLBCL. And recombinant IL-22 protein increased the activation of STAT3 and ERK1/2 in ABC rather than GCB-DLBCL cell lines. For the first time, we suggested the importance of IL-22 and its receptor IL-22R1 pathway in ABC-DLBCL, which warrants further studies.Figure 1. The expression of IL-22R1 in DLBCL cell lines was detected by using immunofluorescence staining. DisclosuresNo relevant conflicts of interest to declare.

The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer.

BackgroundRecently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC).MethodsFlow cytometry was used to determine the expression of interferon gamma (IFN-γ), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-α and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-α were examined.ResultsTh22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-α and IL-6 was significantly high in CC patients.ConclusionsOur results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.

Interleukin-22 (IL-22) Gingival Gene Expression and GCF Concentration in Periodontal Health and Disease

IL-22 is a cytokine that is assumed to improve anti-microbial defense of epidermal and epithelial cells and the cells of gas- trointestinal and respiratory systems. With respect to absence of enough relevant articles in this regard the aim of this study was to evaluate the correlation between IL-22 gene expression in gingival tissues as well as its concentration in GCF and periodontal diseases. Gingival samples obtained from 60 patients of three different groups (healthy, gingivitis and chronic periodontitis) and used for evaluation. Expression of IL-22 mRNA was measured by Real-time PCR and its concentration in GCF was determined by ELISA. In none of the tissue samples, mRNA of IL-22 was detected; However IL-22 concen- tration was significantly higher in periodontitis in comparison to other groups and in gingivitis was higher than the normal gingiva. There was no relationship between concentration of IL-22 in GCF and the extent and severity of chronic peri- odontitis. With respect to the results of this study, probable systemic production of IL-22 in response to periodontopathic bacteria is suspected and it is assumed to counteract with LPS of these bacteria and protect periodontal tissues against adverse effects that results from stimulation of different cells and molecules of immune system by LPS.

Increased urinary interleukin 22 binding protein levels correlate with lupus nephritis activity.

Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE. A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry. Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response. Urinary but not serum IL-22BP levels were associated with active renal disease. Urinary levels of IL-22BP might be a potential marker for the presence of renal involvement in patients with SLE.

Intestine mucosal IL‐22 is reduced following oral probiotic administration: implications on epithelial barrier repair

Interleukin‐22 (IL‐22) is known to play a key regulatory role at mucosal surfaces including the gut. IL‐22 receptor is predominantly expressed on intestinal epithelial cells (IEC) and evidence suggests that IL‐22 can promote intestinal inflammation and mucosal healing. This study demonstrates a role of probiotics in reducing mucosal IL‐22 and investigates the functional role of IL‐22 on IEC in vitro.Rectal biopsies were obtained from active ulcerative colitis patients immediately prior to probiotic (VSL#3) oral administration and approx. 2 months post‐exposure. Biopsies were cultured in complete medium overnight, supernatant collected and spontaneous IL‐22 secretion measured using ELISA. Effects of varying IL‐22 concentration (100ngml−1–1ngml−1) were tested in vitro using both cancer (SW480) and non‐transformed IEC lines. Stimulation was carried out for 48h (proliferation) or 2h (mRNA). A significant reduction in IL‐22 secreted from mucosal biopsies was detected following probiotic treatment (n=9; p&lt;0.03). In our system, addition of IL‐22 to in vitro IEC cultures did not significantly change proliferation rates (n=12, per concentration). IL‐22 induced moderate increases in SOCS3 and TNFα mRNA at the 50ng and 10ng/ml doses.The long‐term effects of IL‐22 on IEC and the predominant source of IL‐22 in the intestinal mucosa will now be investigated.

Th22, but not Th17 Might be a Good Index to Predict the Tissue Involvement of Systemic Lupus Erythematosus

T-helper (Th) cells abnormalities are considered to be associated with the pathogenesis of Systemic lupus erythematosus (SLE). Recently, The Th22 cells have been identified and implicated in the pathogenesis of autoimmune diseases such as Rheumatoid arthritis (RA), although therir role in Systemic lupus erythematosus (SLE) remains unclear. The present study intends to investigate their roles in SLE. Clinical data were collected in 65 SLE patients and 30 healthy controls. The patients were divided into active and inactive groups. CD4(+)IFN-γ(-)IL-17(-)IL-22(+)Tcells (Th22 cells),CD4(+) IFN-γ(-)IL-22(-)IL-17(+)T cells (Th17 cells),and CD4(+) IFN-γ(+) (Th1 cells) were assayed by flow cytometry. Serum interleukin-22 (IL-22) and IL-17 levels were measured by enzyme-linked immunosorbent assay. The main observation focused on increased Th22 cells in patients with sole lupus skin disease and decreased Th22 cells in patients with sole lupus nephritis. Likewise, concentrations of serum IL-22 were increased in patients with sole lupus skin disease, and decreased in patients with sole lupus nephritis. Additionally, there was a positive correlation between the percentage of Th22 cells and IL-22 production. The percentage of Th17 cells or concentration of serum IL-17 correlated positively with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Th22 seems to be a more significant index to predict the tissue involvement of SLE than Th17, although Th17 may play a role in the activity of SLE.

IL-22+CD4+ T-cells in patients with active systemic lupus erythematosus

Interleukin-22 (IL-22) is a regulator of autoimmune diseases. However, the role of IL-22(+)CD4(+) T-cells in the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. This study is aimed at elucidating the potential role of IL-22 and IL-22(+)CD4(+) T-cells in patients with SLE. A total of 22 patients with freshly diagnosed SLE and 18 age-/gender-matched healthy controls (n = 18) were evaluated for the frequency of different types of IL-22-producing CD4(+) T-cells by flow cytometry analysis following in vitro stimulation. The concentrations of plasma IL-22, IL-17A, IFNγ, serum complement factors (C3, C4), C-reactive protein (CRP), antidouble-stranded (ds) DNA and anti-Smith (Sm) antibodies were measured. The potential association among these measures was analyzed. The percentages of IL-22(+)IL-17(-)IFNγ(-), IL-22(+)IL-17A(-)IFN-γ(+), IL-22(-)IL-17(+)IFN-γ(-) and IL-22(+)IL-17(+)IFN-γ(-) CD4(+) T-cells and the levels of plasma IL-22 and IL-17A in the patients were significantly higher than that in the healthy controls (P < 0.01). The frequency of Th22 cells was correlated positively with that of Th17 and IL-22(+)IL-17(+) CD4(+) T-cells, and the frequency of Th17 and IL-22(+)CD4(+) T-cells was correlated positively with the values of SLE disease activity index (SLEDAI), but not with the values of CRP, ERS and C3 in SLE patients. Our data suggest that both Th17 and IL-22(+)CD4(+) T-cells may participate in the pathogenesis of SLE.

Quantitative determination of human interleukin 22 (IL-22) in serum using Singulex-Erenna® Technology

Interleukin-22 (IL-22) is a key mediator of inflammatory processes associated with diseases such as psoriasis, inflammatory bowel disease and rheumatoid arthritis. The measurement of this cytokine in human plasma may provide insight into safety, pharmacodynamics and efficacy of drugs targeting inflammatory pathways. However, commonly used immunoassays are not sufficiently sensitive to measure baseline concentrations of IL-22. Here we describe the analytical validation of an ultrasensitive assay for the measurement of IL-22 in human serum using the Erenna® system by Singulex (Alameda, CA). The lower limit of quantification (LLOQ) of the Erenna assay estimated at 0.2pg/mL was sensitive enough to measure IL-22 in all human serum samples tested. The assay ranged from 0.2 to 100.0pg/mL and showed good dilution linearity. The inter-assay and intra-assay imprecision were <9% and <7% CV respectively. The accuracy determined by spiked recovery in serum samples was >86%. In addition, the results using Erenna assay correlated well with those using the IL-22 Quantikine immunoassay (R&D Systems, Minneapolis, MN) with a coefficient R2 of 0.9285. However the Erenna assay showed an improved sensitivity by approximately 2 logs. These results show that this novel assay offers a significant improvement over previous methods for high-sensitive quantitative measurement of IL-22 in human serum samples.

Role of the Interleukin 10 Family of Cytokines in Patients With Immune Reconstitution Inflammatory Syndrome Associated With HIV Infection and Tuberculosis

Background. The interleukin 10 (IL-10) family comprises cytokines structurally related to IL-10 that share signaling receptors that have conserved signaling cascades. The immunopathogenesis of immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) infection and tuberculosis remains incompletely understood. We hypothesized that a deficiency of IL-10 and its homologs may contribute to the immunopathology of IRIS in these patients.Methods. We performed a case-control analysis involving patients with HIV infection and tuberculosis who had IRIS at clinical presentation (tuberculosis-IRIS) and similar patients with HIV infection and tuberculosis who did not develop tuberculosis-IRIS (non-IRIS). Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 hours. Messenger RNA was analyzed by quantitative reverse transcription polymerase chain reaction analysis. Cytokine concentrations in serum were also determined.Results. Cultures of PBMCs stimulated with M. tuberculosis for 24 hours yielded higher IL-10 and interleukin 22 (IL-22) transcript levels for tuberculosis-IRIS patients, compared with non-IRIS patients. Analysis of corresponding serum samples showed significantly higher concentrations of IL-10 and IL-22 in tuberculosis-IRIS patients, compared with non-IRIS patients.Conclusions. IL-10 and IL-22 were differentially induced in PBMCs from tuberculosis-IRIS patients after in vitro stimulation, and higher concentrations of their corresponding proteins were detected in serum (in vivo). The higher levels of IL-10 observed in this study may represent a compensatory antiinflammatory response during tuberculosis-IRIS. The elevated levels of IL-22 suggest an association between this cytokine and immunopathology during tuberculosis-IRIS.