IL-12 DOWN-REGULATES AUTOANTIBODY PRODUCTION IN MERCURY-INDUCED AUTOIMMUNITY

In genetically susceptible H-2(s) mice, subtoxic doses of mercuric chl oride (HgCl2) induce a complex autoimmune syndrome characterized by th e production of anti-nucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-indu ced autoimmunity in H-2(s) mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, w hich are under IL-4 control, suggests a role for the Th2 subset in thi s syndrome. The IL-12 cytokine induces T cell proliferation and IFN-ga mma production and is necessary for differentiation of naive T cells i nto the Th1 subset, To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effe ct of IL-12 administration in mercury-induced autoimmunity. Groups of ASW mice (H-2(s)) received HgCl2 plus IL-12, HgCl2, alone, or IL-12 al one. IL-12 treatment resulted in a dramatic reduction of the anti-nucl eolar Ab titers, IL-12 also inhibited the HgCl2-induced serum IgG1 inc rease, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice recei ving HgCl2 alone or HgCl2 plus IL-12, Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndro me and that the various manifestations of mercury induced autoimmunity are independently regulated.