Roles of interferon-gamma and interleukin-4 in murine lupus.

Peng SL, Moslehi J, Craft J
J Clin Invest. 1997 99 (8): 1936-46

PMID: 9109438 · PMCID: PMC508018 · DOI:10.1172/JCI119361

The systemic autoimmune syndrome of MRL/Mp-lpr/lpr (MRL/lpr) mice consists of severe pan-isotype hypergammaglobulinemia, autoantibody production, lymphadenopathy, and immune complex-associated end-organ disease. Its pathogenesis has been largely attributed to helper alphabeta T cells that may require critical cytokines to propagate pathogenic autoantibody production. To investigate the roles of prototypical Th1 and Th2 cytokines in the pathogenesis of murine lupus, IFN-gamma -/- and IL-4 -/- lupus-prone mice were generated by backcrossing cytokine knockout animals against MRL/lpr breeders. IFN-gamma -/- animals produced significantly reduced titers of IgG2a and IgG2b serum immunoglobulins as well as autoantibodies, but maintained comparable levels of IgG1 and IgE in comparison to cytokine-intact controls; in contrast, IL-4 -/- animals produced significantly less IgG1 and IgE serum immunoglobulins, but maintained comparable levels of IgG2a and IgG2b as well as autoantibodies in comparison to controls. Both IFN-gamma -/- and IL-4 -/- mice, however, developed significantly reduced lymphadenopathy and end-organ disease. These results suggest that IFN-gamma and IL-4 play opposing but dispensable roles in the development of lupus-associated hypergammaglobulinemia and autoantibody production; however, they both play prominent roles in the pathogenesis of murine lupus-associated tissue injury, as well as in lpr-induced lymphadenopathy.

MeSH Terms (17)

Animals Autoantibodies Female Immunoglobulin Isotypes Interferon-gamma Interleukin-4 Kidney Liver Lupus Erythematosus, Systemic Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Inbred MRL lpr Mice, Knockout Mutation Salivary Glands

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