IFN-beta-1b inhibits IL-12 production in peripheral blood mononuclear cells in an IL-10-dependent mechanism: relevance to IFN-beta-1b therapeutic effects in multiple sclerosis.
IL-12 is a proinflammatory cytokine secreted by dendritic cells in response to microbial Ags and mitogens. IL-12 is thought to contribute to the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). This is based on studies in experimental allergic encephalomyelitis and the demonstration that PBMC IL-12 production correlates with disease progression in MS. IFN-beta-1b is an effective treatment for MS, which is thought to involve in part inhibition of proinflammatory cytokines. In this study we examined the effect of in vitro treatment with IFN-beta-1b, on mitogen-induced IL-12 production in human PBMC and myelin basic protein-specific T cell lines obtained from healthy donors and MS patients. We demonstrate that IFN-beta-1b significantly inhibits inducible IL-12 p40 up to 80% and biologically active IL-12 p70 up to 70% beginning at a dose of 10 IU/ml. This inhibition is IL-10 dependent, as it could be blocked by anti-IL-10 but not anti-IL-4 or control Abs. Thus, endogenously produced IL-10 is a required cofactor for the IFN-beta-1b inhibitory effect on IL-12 to occur. We conclude that IFN-beta-1b has a profound inhibitory effect on PBMC IL-12 production in vitro, and that this effect is IL-10 dependent. These findings are potentially relevant to the therapeutic mechanism of IFN-beta-1b in MS.
Wang
X
X
Department of Neurology, University of Maryland, Baltimore, MD 21201, USA.
Chen
M
M
Wandinger
K P
KP
Williams
G
G
Dhib-Jalbut
S
S
D002460:Cell Line; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D004676:Myelin Basic Protein / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D016753:Interleukin-10; D000068576:Interferon beta-1b; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a