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Gene Review

IL10  -  interleukin 10

Homo sapiens

Synonyms: CSIF, Cytokine synthesis inhibitory factor, GVHDS, IL-10, IL10A, ...
 
 
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Disease relevance of IL10

 

Psychiatry related information on IL10

 

High impact information on IL10

 

Chemical compound and disease context of IL10

 

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

 

Enzymatic interactions of IL10

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

Regulatory relationships of IL10

 

Other interactions of IL10

 

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

  1. Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Shin, H.D., Winkler, C., Stephens, J.C., Bream, J., Young, H., Goedert, J.J., O'Brien, T.R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinaldo, C., Donfield, S., Willoughby, A., O'Brien, S.J., Smith, M.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes. Sicinschi, L.A., Lopez-Carrillo, L., Camargo, M.C., Correa, P., Sierra, R.A., Henry, R.R., Chen, J., Zabaleta, J., Piazuelo, M.B., Schneider, B.G. Int. J. Cancer (2006) [Pubmed]
  3. Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis. Wilson, J., Rowlands, K., Rockett, K., Moore, C., Lockhart, E., Sharland, M., Kwiatkowski, D., Hull, J. J. Infect. Dis. (2005) [Pubmed]
  4. CD40/CD40L interactions and cytokines regulate HIV replication in B cells in vitro. Gras, G., Legendre, C., Krzysiek, R., Dormont, D., Galanaud, P., Richard, Y. Virology (1996) [Pubmed]
  5. Tumour necrosis factor-alpha polymorphism and the HLA-Cw*0602 allele in psoriatic arthritis. Al-Heresh, A.M., Proctor, J., Jones, S.M., Dixey, J., Cox, B., Welsh, K., McHugh, N. Rheumatology (Oxford, England) (2002) [Pubmed]
  6. Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum. Arnaud, V., Li, J., Wang, Y., Fu, X., Mengzhi, S., Luo, X., Hou, X., Dessein, H., Jie, Z., Xin-Ling, Y., He, H., McManus, D.P., Li, Y., Dessein, A. J. Infect. Dis. (2008) [Pubmed]
  7. Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome. Pachkoria, K., Lucena, M.I., Crespo, E., Ruiz-Cabello, F., Lopez-Ortega, S., Fernandez, M.A., Romero-Gomez, M., Madrazo, A., Durán, J.A., de Dios, A.M., Borraz, Y., Navarro, J.M., Andrade, R.J. J. Hepatol. (2008) [Pubmed]
  8. Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis. Kaplan, D.E., Ikeda, F., Li, Y., Nakamoto, N., Ganesan, S., Valiga, M.E., Nunes, F.A., Rajender Reddy, K., Chang, K.M. J. Hepatol. (2008) [Pubmed]
  9. Interaction between BCL2 and interleukin-10 gene polymorphisms alter outcomes of diffuse large B-cell lymphoma following rituximab plus CHOP chemotherapy. Park, Y.H., Sohn, S.K., Kim, J.G., Lee, M.H., Song, H.S., Kim, M.K., Jung, J.S., Lee, J.J., Kim, H.J., Kim, D.H. Clin. Cancer Res. (2009) [Pubmed]
  10. Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy. Costa, G.C., da Costa Rocha, M.O., Moreira, P.R., Menezes, C.A., Silva, M.R., Gollob, K.J., Dutra, W.O. J. Infect. Dis. (2009) [Pubmed]
  11. Moderate alcohol intake in humans attenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Mandrekar, P., Catalano, D., White, B., Szabo, G. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  12. Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease. Arosio, B., Trabattoni, D., Galimberti, L., Bucciarelli, P., Fasano, F., Calabresi, C., Cazzullo, C.L., Vergani, C., Annoni, G., Clerici, M. Neurobiol. Aging (2004) [Pubmed]
  13. Interleukin 4 and interleukin 10 levels are elevated in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Stoeck, K., Bodemer, M., Ciesielczyk, B., Meissner, B., Bartl, M., Heinemann, U., Zerr, I. Arch. Neurol. (2005) [Pubmed]
  14. Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Capuron, L., Ravaud, A., Gualde, N., Bosmans, E., Dantzer, R., Maes, M., Neveu, P.J. Psychoneuroendocrinology (2001) [Pubmed]
  15. Interleukin-10 and the interleukin-10 receptor. Moore, K.W., de Waal Malefyt, R., Coffman, R.L., O'Garra, A. Annu. Rev. Immunol. (2001) [Pubmed]
  16. The CD40 antigen and its ligand. Banchereau, J., Bazan, F., Blanchard, D., Brière, F., Galizzi, J.P., van Kooten, C., Liu, Y.J., Rousset, F., Saeland, S. Annu. Rev. Immunol. (1994) [Pubmed]
  17. Interleukin-10. Moore, K.W., O'Garra, A., de Waal Malefyt, R., Vieira, P., Mosmann, T.R. Annu. Rev. Immunol. (1993) [Pubmed]
  18. Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C. Panasiuk, A., Prokopowicz, D., Panasiuk, B. World J. Gastroenterol. (2004) [Pubmed]
  19. Interferon gamma inhibits interleukin 10 production by monocytes. Chomarat, P., Rissoan, M.C., Banchereau, J., Miossec, P. J. Exp. Med. (1993) [Pubmed]
  20. Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Shkoda, A., Ruiz, P.A., Daniel, H., Kim, S.C., Rogler, G., Sartor, R.B., Haller, D. Gastroenterology (2007) [Pubmed]
  21. Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Keel, M., Ungethüm, U., Steckholzer, U., Niederer, E., Hartung, T., Trentz, O., Ertel, W. Blood (1997) [Pubmed]
  22. Interleukin-10 is a protective factor against diet-induced insulin resistance in liver. Cintra, D.E., Pauli, J.R., Araújo, E.P., Moraes, J.C., de Souza, C.T., Milanski, M., Morari, J., Gambero, A., Saad, M.J., Velloso, L.A. J. Hepatol. (2008) [Pubmed]
  23. Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma. Shin, H.D., Park, B.L., Kim, L.H., Jung, J.H., Kim, J.Y., Yoon, J.H., Kim, Y.J., Lee, H.S. Hum. Mol. Genet. (2003) [Pubmed]
  24. Anemia after late introduction of sirolimus may correlate with biochemical evidence of a chronic inflammatory state. Thaunat, O., Beaumont, C., Chatenoud, L., Lechaton, S., Mamzer-Bruneel, M.F., Varet, B., Kreis, H., Morelon, E. Transplantation (2005) [Pubmed]
  25. The immune suppressive effect of dexamethasone in rheumatoid arthritis is accompanied by upregulation of interleukin 10 and by differential changes in interferon gamma and interleukin 4 production. Verhoef, C.M., van Roon, J.A., Vianen, M.E., Lafeber, F.P., Bijlsma, J.W. Ann. Rheum. Dis. (1999) [Pubmed]
  26. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Keller, C., Webb, A., Davis, J. Ann. Rheum. Dis. (2003) [Pubmed]
  27. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Rudwaleit, M., Yin, Z., Siegert, S., Grolms, M., Radbruch, A., Braun, J., Sieper, J. Ann. Rheum. Dis. (2000) [Pubmed]
  28. Interleukin 10 inhibits cytokine production of human AML cells. Westermann, F., Kube, D., Haier, B., Bohlen, H., Engert, A., Zuehlsdorf, M., Diehl, V., Tesch, H. Ann. Oncol. (1996) [Pubmed]
  29. Flow cytometric analysis of gut mucosal lymphocytes supports an impaired Th1 cytokine profile in spondyloarthropathy. Van Damme, N., De Vos, M., Baeten, D., Demetter, P., Mielants, H., Verbruggen, G., Cuvelier, C., Veys, E.M., De Keyser, F. Ann. Rheum. Dis. (2001) [Pubmed]
  30. Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10. Milligan, E.D., Langer, S.J., Sloane, E.M., He, L., Wieseler-Frank, J., O'Connor, K., Martin, D., Forsayeth, J.R., Maier, S.F., Johnson, K., Chavez, R.A., Leinwand, L.A., Watkins, L.R. Eur. J. Neurosci. (2005) [Pubmed]
  31. IL10 resistant PGS2 expression in at-risk/Type 1 diabetic human monocytes. Litherland, S.A., Xie, T.X., Grebe, K.M., Li, Y., Moldawer, L.L., Clare-Salzler, M.J. J. Autoimmun. (2004) [Pubmed]
  32. Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFalpha. Baeten, D., Van Damme, N., Van den Bosch, F., Kruithof, E., De Vos, M., Mielants, H., Veys, E.M., De Keyser, F. Ann. Rheum. Dis. (2001) [Pubmed]
  33. Dehydroepiandrosterone suppresses interleukin 10 synthesis in women with systemic lupus erythematosus. Chang, D.M., Chu, S.J., Chen, H.C., Kuo, S.Y., Lai, J.H. Ann. Rheum. Dis. (2004) [Pubmed]
  34. L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes. Zea, A.H., Rodriguez, P.C., Culotta, K.S., Hernandez, C.P., DeSalvo, J., Ochoa, J.B., Park, H.J., Zabaleta, J., Ochoa, A.C. Cell. Immunol. (2004) [Pubmed]
  35. Identification and functional characterization of a second chain of the interleukin-10 receptor complex. Kotenko, S.V., Krause, C.D., Izotova, L.S., Pollack, B.P., Wu, W., Pestka, S. EMBO J. (1997) [Pubmed]
  36. 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. Barcellini, W., Rizzardi, G.P., Marriott, J.B., Fain, C., Shattock, R.J., Meroni, P.L., Poli, G., Dalgleish, A.G. AIDS (1996) [Pubmed]
  37. Inhibition of IL-10 expression by IFN-gamma up-regulates transcription of TNF-alpha in human monocytes. Donnelly, R.P., Freeman, S.L., Hayes, M.P. J. Immunol. (1995) [Pubmed]
  38. 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. Mori, N., Prager, D. Eur. J. Haematol. (1997) [Pubmed]
  39. Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines. Stearns, M.E., Wang, M., Hu, Y., Garcia, F.U., Rhim, J. Clin. Cancer Res. (2003) [Pubmed]
  40. Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling. Samarasinghe, R., Tailor, P., Tamura, T., Kaisho, T., Akira, S., Ozato, K. J. Interferon Cytokine Res. (2006) [Pubmed]
  41. Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes. Malisan, F., Brière, F., Bridon, J.M., Harindranath, N., Mills, F.C., Max, E.E., Banchereau, J., Martinez-Valdez, H. J. Exp. Med. (1996) [Pubmed]
  42. Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. Cassatella, M.A., Meda, L., Gasperini, S., Calzetti, F., Bonora, S. J. Exp. Med. (1994) [Pubmed]
  43. Interleukin-10 upregulates tumor necrosis factor receptor type-II (p75) gene expression in endotoxin-stimulated human monocytes. Dickensheets, H.L., Freeman, S.L., Smith, M.F., Donnelly, R.P. Blood (1997) [Pubmed]
  44. Interleukin-10 inhibits interleukin-8 production in human neutrophils. Wang, P., Wu, P., Anthes, J.C., Siegel, M.I., Egan, R.W., Billah, M.M. Blood (1994) [Pubmed]
  45. Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. Nylén, S., Maurya, R., Eidsmo, L., Manandhar, K.D., Sundar, S., Sacks, D. J. Exp. Med. (2007) [Pubmed]
  46. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. Randow, F., Syrbe, U., Meisel, C., Krausch, D., Zuckermann, H., Platzer, C., Volk, H.D. J. Exp. Med. (1995) [Pubmed]
  47. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. Katsikis, P.D., Chu, C.Q., Brennan, F.M., Maini, R.N., Feldmann, M. J. Exp. Med. (1994) [Pubmed]
  48. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. Groux, H., Bigler, M., de Vries, J.E., Roncarolo, M.G. J. Exp. Med. (1996) [Pubmed]
  49. Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs. Matthes, T., Werner-Favre, C., Tang, H., Zhang, X., Kindler, V., Zubler, R.H. J. Exp. Med. (1993) [Pubmed]
  50. Atopic dermatitis is associated with a low-producer transforming growth factor beta(1) cytokine genotype. Arkwright, P.D., Chase, J.M., Babbage, S., Pravica, V., David, T.J., Hutchinson, I.V. J. Allergy Clin. Immunol. (2001) [Pubmed]
  51. Interleukin 10-2849AA genotype protects against pre-eclampsia. de Groot, C.J., Jansen, M.W., Bertina, R.M., Schonkeren, J.J., Helmerhorst, F.M., Huizinga, T.W. Genes Immun. (2004) [Pubmed]
  52. Late onset reactions to oral food challenge are linked to low serum interleukin-10 concentrations in patients with atopic dermatitis and food allergy. Sütas, Y., Kekki, O.M., Isolauri, E. Clin. Exp. Allergy (2000) [Pubmed]
 
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