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Gene Review

Il10  -  interleukin 10

Mus musculus

Synonyms: CSIF, Cytokine synthesis inhibitory factor, IL-10, Il-10, Interleukin-10, ...
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Disease relevance of Il10

  • We report that colitis was dependent on TLR signaling in Il10(-/-) mice [1].
  • Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice [2].
  • Experiments using Il10 knockout mice, for which no differences between the susceptibilities of males and females to Listeria infection could be detected, confirmed the important role of this immunosuppressive cytokine for the outcome of disease [3].
  • These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent [4].
  • Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates in the colon and shares histopathological features with human IBD [5].
  • We demonstrate that increased IL-13 receptor alpha 2 (IL-13Ralpha2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice [6].
  • These data demonstrate that P. gingivalis-induced periodontitis in IL-10-deficient mice is dependent upon IL-12p40-mediated proinflammatory T cell responses [7].

Psychiatry related information on Il10


High impact information on Il10


Chemical compound and disease context of Il10


Genetic context of IL-10



Biological context of Il10

  • In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes [2].
  • In addition, three main effect QTLs on chromosomes 4, 5, and 12 were identified in the backcross to C57BL/6J-Il10(-/-) [20].
  • It further shows that caution should be observed when analyzing the effects of knockout/congenic strains because many of the gene expression differences in these comparisons could not be attributable to the ablated Il10 gene but rather to passenger gene effects [21].
  • Finally, IL-10 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to IL-4 [22].
  • These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10 [23].

Anatomical context of Il10

  • Genetic removal of Il10 resulted in the maintenance of robust effector T-cell responses, the rapid elimination of virus and the development of antiviral memory T-cell responses [24].
  • ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10 [25].
  • However, these CD8- cells produced large amounts of IL-4, IL-5, and IL-10 and helped activate resting B cells [26].
  • Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels [23].
  • In further studies in vitro, it was shown that IL-10 blocked the ability of IFN-gamma to inhibit the intracellular replication of T. cruzi in mouse peritoneal macrophages [27].

Associations of Il10 with chemical compounds


Physical interactions of Il10


Regulatory relationships of Il10


Other interactions of Il10

  • Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected [40].
  • The protective effect of IL-10 was reversed by prior injection of neutralizing anti-IL-10 antibodies, and correlated with a substantial decrease in endotoxin-induced TNF-alpha release [4].
  • Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected [41].
  • Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice [42].
  • Decreased graft survival in IL-10 -/- recipients was associated with increases in iNOS and IFN-gamma-driven responses [43].

Analytical, diagnostic and therapeutic context of Il10


  1. Role of toll-like receptors in spontaneous commensal-dependent colitis. Rakoff-Nahoum, S., Hao, L., Medzhitov, R. Immunity (2006) [Pubmed]
  2. Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. Ko, K.S., Lee, M., Koh, J.J., Kim, S.W. Mol. Ther. (2001) [Pubmed]
  3. Sex-dependent susceptibility to Listeria monocytogenes infection is mediated by differential interleukin-10 production. Pasche, B., Kalaydjiev, S., Franz, T.J., Kremmer, E., Gailus-Durner, V., Fuchs, H., Hrabé de Angelis, M., Lengeling, A., Busch, D.H. Infect. Immun. (2005) [Pubmed]
  4. Interleukin 10 protects mice from lethal endotoxemia. Howard, M., Muchamuel, T., Andrade, S., Menon, S. J. Exp. Med. (1993) [Pubmed]
  5. T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. Davidson, N.J., Leach, M.W., Fort, M.M., Thompson-Snipes, L., Kühn, R., Müller, W., Berg, D.J., Rennick, D.M. J. Exp. Med. (1996) [Pubmed]
  6. IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. Wilson, M.S., Elnekave, E., Mentink-Kane, M.M., Hodges, M.G., Pesce, J.T., Ramalingam, T.R., Thompson, R.W., Kamanaka, M., Flavell, R.A., Keane-Myers, A., Cheever, A.W., Wynn, T.A. J. Clin. Invest. (2007) [Pubmed]
  7. T cell response mediated by myeloid cell-derived IL-12 is responsible for Porphyromonas gingivalis-induced periodontitis in IL-10-deficient mice. Sasaki, H., Suzuki, N., Kent, R., Kawashima, N., Takeda, J., Stashenko, P. J. Immunol. (2008) [Pubmed]
  8. Use of perphenazine to control cannibalism in DBA/1 mice. Carter, D.B., Kennett, M.J., Franklin, C.L. Comp. Med. (2002) [Pubmed]
  9. Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice. Toth, L.A., Opp, M.R. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  10. Interleukin-10 (IL-10) but not Lipopolysaccharide (LPS) produces increased motor activity and abnormal exploratory patterns while impairing spatial learning in Balb/c mice. Harvey, D., Smith, R., English, K., Mahon, B., Commins, S. Physiol. Behav. (2006) [Pubmed]
  11. Differential regulation of murine T lymphocyte subsets. Fitch, F.W., McKisic, M.D., Lancki, D.W., Gajewski, T.F. Annu. Rev. Immunol. (1993) [Pubmed]
  12. Interleukin-10-deficient mice develop chronic enterocolitis. Kühn, R., Löhler, J., Rennick, D., Rajewsky, K., Müller, W. Cell (1993) [Pubmed]
  13. Reciprocal CD40 signals through p38MAPK and ERK-1/2 induce counteracting immune responses. Mathur, R.K., Awasthi, A., Wadhone, P., Ramanamurthy, B., Saha, B. Nat. Med. (2004) [Pubmed]
  14. Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice. Abe, T., Arai, T., Ogawa, A., Hiromatsu, T., Masuda, A., Matsuguchi, T., Nimura, Y., Yoshikai, Y. Hepatology (2004) [Pubmed]
  15. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Louis, H., Van Laethem, J.L., Wu, W., Quertinmont, E., Degraef, C., Van den Berg, K., Demols, A., Goldman, M., Le Moine, O., Geerts, A., Devière, J. Hepatology (1998) [Pubmed]
  16. Substance P regulates Th1-type colitis in IL-10 knockout mice. Weinstock, J.V., Blum, A., Metwali, A., Elliott, D., Bunnett, N., Arsenescu, R. J. Immunol. (2003) [Pubmed]
  17. Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Elliott, D.E., Setiawan, T., Metwali, A., Blum, A., Urban, J.F., Weinstock, J.V. Eur. J. Immunol. (2004) [Pubmed]
  18. The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency. Lytle, C., Tod, T.J., Vo, K.T., Lee, J.W., Atkinson, R.D., Straus, D.S. Inflamm. Bowel Dis. (2005) [Pubmed]
  19. The production of two Th2 cytokines, interleukin-4 and interleukin-10, is controlled independently by locus Cypr1 and by loci Cypr2 and Cypr3, respectively. Kosarová, M., Havelková, H., Krulová, M., Demant, P., Lipoldová, M. Immunogenetics. (1999) [Pubmed]
  20. Genetics of colitis susceptibility in IL-10-deficient mice: backcross versus F2 results contrasted by principal component analysis. Mähler, M., Most, C., Schmidtke, S., Sundberg, J.P., Li, R., Hedrich, H.J., Churchill, G.A. Genomics (2002) [Pubmed]
  21. Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic strains and candidate gene identification studies. de Ledesma, A.M., Desai, A.N., Bolivar, V.J., Symula, D.J., Flaherty, L. Mamm. Genome (2006) [Pubmed]
  22. Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. Go, N.F., Castle, B.E., Barrett, R., Kastelein, R., Dang, W., Mosmann, T.R., Moore, K.W., Howard, M. J. Exp. Med. (1990) [Pubmed]
  23. Altered immune responses in interleukin 10 transgenic mice. Hagenbaugh, A., Sharma, S., Dubinett, S.M., Wei, S.H., Aranda, R., Cheroutre, H., Fowell, D.J., Binder, S., Tsao, B., Locksley, R.M., Moore, K.W., Kronenberg, M. J. Exp. Med. (1997) [Pubmed]
  24. Interleukin-10 determines viral clearance or persistence in vivo. Brooks, D.G., Trifilo, M.J., Edelmann, K.H., Teyton, L., McGavern, D.B., Oldstone, M.B. Nat. Med. (2006) [Pubmed]
  25. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Lumeng, C.N., Bodzin, J.L., Saltiel, A.R. J. Clin. Invest. (2007) [Pubmed]
  26. Switch of CD8 T cells to noncytolytic CD8-CD4- cells that make TH2 cytokines and help B cells. Erard, F., Wild, M.T., Garcia-Sanz, J.A., Le Gros, G. Science (1993) [Pubmed]
  27. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. Silva, J.S., Morrissey, P.J., Grabstein, K.H., Mohler, K.M., Anderson, D., Reed, S.G. J. Exp. Med. (1992) [Pubmed]
  28. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Lee, T.S., Chau, L.Y. Nat. Med. (2002) [Pubmed]
  29. IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways. O'Farrell, A.M., Liu, Y., Moore, K.W., Mui, A.L. EMBO J. (1998) [Pubmed]
  30. Interleukin 4 suppresses c-kit ligand-induced expression of cytosolic phospholipase A2 and prostaglandin endoperoxide synthase 2 and their roles in separate pathways of eicosanoid synthesis in mouse bone marrow-derived mast cells. Murakami, M., Penrose, J.F., Urade, Y., Austen, K.F., Arm, J.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  31. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Bhattacharyya, S., Sen, P., Wallet, M., Long, B., Baldwin, A.S., Tisch, R. Blood (2004) [Pubmed]
  32. IL-10 induces regulatory T cell apoptosis by up-regulation of the membrane form of TNF-alpha. Marra, L.E., Zhang, Z.X., Joe, B., Campbell, J., Levy, G.A., Penninger, J., Zhang, L. J. Immunol. (2004) [Pubmed]
  33. Direct interaction of C/EBPdelta and Sp1 at the GC-enriched promoter region synergizes the IL-10 gene transcription in mouse macrophage. Chiang, B.T., Liu, Y.W., Chen, B.K., Wang, J.M., Chang, W.C. J. Biomed. Sci. (2006) [Pubmed]
  34. Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice. Hansson, A.S., Johansson, A.C., Holmdahl, R. Arthritis Res. Ther. (2004) [Pubmed]
  35. Post-transcriptional stabilization by interleukin-1beta of interleukin-6 mRNA induced by c-kit ligand and interleukin-10 in mouse bone marrow-derived mast cells. Lu-Kuo, J.M., Austen, K.F., Katz, H.R. J. Biol. Chem. (1996) [Pubmed]
  36. The IkappaB protein Bcl-3 negatively regulates transcription of the IL-10 gene in macrophages. Riemann, M., Endres, R., Liptay, S., Pfeffer, K., Schmid, R.M. J. Immunol. (2005) [Pubmed]
  37. Role of interleukin-4 (IL-4) and IL-10 in serum immunoglobulin G antibody responses following mucosal or systemic reovirus infection. Mathers, A.R., Cuff, C.F. J. Virol. (2004) [Pubmed]
  38. Regulation of the mRNA expression for tumor necrosis factor-alpha in rat liver macrophages. Grewe, M., Gausling, R., Gyufko, K., Hoffmann, R., Decker, K. J. Hepatol. (1994) [Pubmed]
  39. Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Stämpfli, M.R., Cwiartka, M., Gajewska, B.U., Alvarez, D., Ritz, S.A., Inman, M.D., Xing, Z., Jordana, M. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  40. Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis. Tarrant, T.K., Silver, P.B., Wahlsten, J.L., Rizzo, L.V., Chan, C.C., Wiggert, B., Caspi, R.R. J. Exp. Med. (1999) [Pubmed]
  41. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. Fiorentino, D.F., Bond, M.W., Mosmann, T.R. J. Exp. Med. (1989) [Pubmed]
  42. Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. Hata, H., Sakaguchi, N., Yoshitomi, H., Iwakura, Y., Sekikawa, K., Azuma, Y., Kanai, C., Moriizumi, E., Nomura, T., Nakamura, T., Sakaguchi, S. J. Clin. Invest. (2004) [Pubmed]
  43. Heart transplants in interferon-gamma, interleukin 4, and interleukin 10 knockout mice. Recipient environment alters graft rejection. Räisänen-Sokolowski, A., Mottram, P.L., Glysing-Jensen, T., Satoskar, A., Russell, M.E. J. Clin. Invest. (1997) [Pubmed]
  44. Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. Kasama, T., Strieter, R.M., Lukacs, N.W., Lincoln, P.M., Burdick, M.D., Kunkel, S.L. J. Clin. Invest. (1995) [Pubmed]
  45. Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer. Kundu, N., Beaty, T.L., Jackson, M.J., Fulton, A.M. J. Natl. Cancer Inst. (1996) [Pubmed]
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