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

SL Peng, J Moslehi, J Craft - The Journal of clinical …, 1997 - Am Soc Clin Investig
The Journal of clinical investigation, 1997Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation