| First Author | Peng SL | Year | 1997 |
| Journal | J Clin Invest | Volume | 99 |
| Issue | 8 | Pages | 1936-46 |
| PubMed ID | 9109438 | Mgi Jnum | J:39600 |
| Mgi Id | MGI:86954 | Doi | 10.1172/JCI119361 |
| Citation | Peng SL, et al. (1997) Roles of interferon-gamma and interleukin-4 in murine lupus. J Clin Invest 99(8):1936-46 |
| abstractText | 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 alpha beta 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. |
