Disease relevance of IL10

• Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10 [1].
• Several polymorphisms of the IL1B and IL10 gene promoters have been reported to be associated with gastric cancer risk in Caucasians [2].
• Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis [3].
• In contrast, IL10 down-regulated HIV replication induced by cytokines, without affecting spontaneous or CD40 Ab-induced replication [4].
• OBJECTIVES: To investigate polymorphisms in the genes for tumour necrosis factor alpha (TNFA), interleukin 10 (IL10) and tumour necrosis factor receptor II (TNFRII) in patients with psoriatic arthritis (PsA) and their relationship to the HLA-Cw*0602 allele and to the ages at onset of psoriasis and arthritis and the pattern of joint involvement [5].
• IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects [6].
• Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI [7].
• Both HCV-specific IL-10 and IFNgamma responses were detected early within 1-2 months of acute clinical hepatitis C [8].
• These data indicated that R-CHOP chemotherapy resistance in diffuse large B-cell lymphoma may involve interactions between the BCL2 and IL10 genes [9].
• The IL-10 gene polymorphism and IL-10 expression are important in determining susceptibility to chagasic cardiomyopathy [10].

Psychiatry related information on IL10

• CONCLUSIONS: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF-kappaB [11].
• Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease [12].
• RESULTS: Interleukin 10 levels were significantly elevated in the cerebrospinal fluid of CJD patients (median, 9.8 pg/mL) [13].
• OBJECTIVE: To obtain data on anti-inflammatory cytokines interleukin 4 and interleukin 10 in the cerebrospinal fluid of patients with CJD, patients with other dementia, and nondemented neurological patients and controls [13].
• In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint [14].

High impact information on IL10

• Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types [15].
• In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells [15].
• Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses [15].
• Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation [16].
• In addition, IL-10 likely contributes to regulating proliferation and differentiation of B cells, mast cells, and thymocytes [17].

Chemical compound and disease context of IL10

• METHODS: Concentrations of MCP-1, soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1), sP-selectin, interleukin (IL) 6, and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0, 16, 32, 48 wk of the therapy [18].
• Herein, we studied the balance between IFN-gamma and IL-10 production by human peripheral blood mononuclear cells (PBMC) in response to Staphylococcus aureus Cowan (SAC) or lipopolysaccharide (LPS) [19].
• RESULTS: Primary IEC from IL-10-/- mice as well as inflammatory bowel disease patients revealed increased expression levels of the glucose-regulated ER stress protein (grp)-78 under conditions of chronic inflammation [20].
• METHODS: Primary IEC were isolated from Enterococcus faecalis-monoassociated IL-10-deficient (IL-10-/-) and wild-type mice to perform 2D-gel sodium-dodecyl-sulfate polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry [20].
• Reduced neutrophil apoptosis during sepsis was concomitant with increased tyrosine phosphorylation, while IL-10 markedly inhibited tyrosine phosphorylation in LPS-stimulated neutrophils [21].
• In an animal model of diet-induced fatty liver disease, the inhibition of IL-10 promotes the increased expression of inflammatory cytokines, the worsening of insulin signaling and the activation of gluconeogenic and lipidogenic pathways [22].

Biological context of IL10

• An estimated 25-30% of long-term nonprogressors (who avoid clinical AIDS for 10 or more years after HIV-1 infection) can be attributed to their IL10-+/+ promoter genotype [1].
• Genetic association analysis of a well-characterized HBV cohort revealed that one of IL10 haplotypes, IL10-ht2, was strongly associated with hepatocellular carcinoma (HCC) occurrence in gene dose-dependent manner [23].
• CONCLUSIONS: Late introduction of SRL may induce anemia and correlates with biochemical evidence of a chronic inflammatory state possibly due to defective IL10-dependent inflammatory autoregulation [24].
• The upregulation of IL10 production may be involved in the prolonged clinical benefit [25].
• However, other studies report a down regulation of these cytokines in the SpA, with a relative anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10) [26].

Anatomical context of IL10

• Inversely, IL10 positive T cells increased from a median of 0.65% (interquartile range 0.6-0.93%) to a median of 1 [27].
• IL10 inhibits cytokine production of activated macrophages and T-helper 1 cells [28].
• OBJECTIVE: To quantify the fraction of gut mucosal lymphocytes expressing the T helper type 1 (Th1) cytokines, interferon gamma (IFNgamma) and interleukin (IL)2, and the Th2 cytokines, IL4 and IL10, at the single cell level in patients with spondyloarthropathy (SpA) in comparison with healthy controls [29].
• Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far less human IL-10 observed in cervical CSF [30].
• IL10 resistant PGS2 expression in at-risk/Type 1 diabetic human monocytes [31].

Associations of IL10 with chemical compounds

• IL10 production increased after dexamethasone treatment and this was sustained for at least six weeks [25].
• After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry [32].
• In contrast, IL10 significantly inhibited the cytokine production at the mRNA and protein level and spontaneous thymidine uptake in a dose-dependent way [28].
• IL10 demonstrated a greater and significant reduction from baseline (9.21 (9.66) to 1.89 (1.47) pg/ml in the DHEA treatment group) [33].
• In contrast, T cells stimulated and cultured in absence of L-arginine, present a sustained down-regulation of CD3zeta preventing the normal expression of the TCR, exhibit a decreased proliferation, and a significantly diminished production of IFNgamma, IL5, and IL10, but not IL2 [34].

Physical interactions of IL10

• We report here that, although human IL-10 binds to the human IL-10R1 chain expressed in hamster cells, it does not induce signal transduction [35].
• Interleukin-10-induced HIV-1 expression is mediated by induction of both membrane-bound tumour necrosis factor (TNF)-alpha and TNF receptor type 1 in a promonocytic cell line [36].
• Thus, potentiation of TNF-alpha production by IFN-gamma in monocytes is coupled to inhibition of endogenous IL-10 expression [37].
• Activation of the interleukin-10 gene in the human T lymphoma line HuT 78: identification and characterization of NF-kappa B binding sites in the regulatory region of the interleukin-10 gene [38].
• Electrophoretic mobility shift assays revealed that IL-10 induced protein(s) binding to a putative "silencer element" (-1309 to -555 fragment) downstream of the p53 binding site (-1649 to -1640) [39].

Enzymatic interactions of IL10

• Further, Stat3 was phosphorylated and bound to the IL-10 promoter in TLR-stimulated DCs [40].

Regulatory relationships of IL10

• Interleukin 10 (IL-10) was first described for its ability to inhibit interferon gamma (IFN-gamma) production [19].
• Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes [41].
• Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation [42].
• Together, these findings demonstrate that IL-10 coordinately downregulates expression of TNF-alpha and upregulates expression of TNF-RII, particularly the soluble form of this receptor, in monocytes [43].
• Interleukin-10 inhibits interleukin-8 production in human neutrophils [44].
• Splenic T cells depleted of CD25(+) cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen [45].

Other interactions of IL10

• In vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of monocytes from septic patients with fatal outcome: downregulation of LPS-induced TNF-alpha and IL-10 production but not of IL-1RA secretion [46].
• In contrast, among various cytokines, only IFN-gamma strongly reduced IL-10 synthesis by SAC- or LPS-activated PBMC and monocytes [19].
• IL-8 levels were reduced by day 5; however, IL-6 levels were not affected by exogenous IL-10 [47].
• The anergic T cells failed to produce IL-2, IL-5, IL-10, interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor [48].
• Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA [49].

Analytical, diagnostic and therapeutic context of IL10

• METHODS: Using amplification refractory mutation screening PCR, we examined TGFB1 and IL10 gene polymorphisms, which are known to affect cytokine production, in 68 children with moderately severe AD and in 50 nonatopic children [50].
• The levels of cytokines including interleukin (IL) 1, IL2, interferon gamma, IL4, and IL10 were determined by ELISA [33].
• Only IL1beta and IL10 could be detected in the serum of lupus patients; however, there was no significant mean (SD) difference in serum IL1beta before and after treatment (9.94 (8.92) v 9.20 (6.49) pg/ml) [33].
• Therefore, we tested the hypothesis that pre-eclampsia is associated with genetic variation in the IL10 promoter region in a case-control study for pre-eclampsia [51].
• The late-reacting cases had more positive skin patch test and negative skin prick test reactivities with allergenic food, and they had lower serum IL10 concentrations than immediate-reacting cases [52].

References