Interleukin-12 enhances clinical experimental autoimmune myasthenia gravis in susceptible but not resistant mice

Abstract

Experimental autoimmune myasthenia gravis (EAMG) is induced by antibodies against the nicotinic acetylcholine receptor (AChR). Studies indicate a role for interferon-γ (IFN-γ) in EAMG. We examined the effect of IL-12, a major inducer of IFN-γ production, on EAMG in C57BL/6 mice. Five doses of IL-12 accelerated and enhanced clinical disease in AChR-immunized mice. Control B6 mice, IFN-γ gene-knockout mice, and EAMG-resistant bm12 mice showed no enhancement of disease. Shifting to a Th1-type antibody isotype distribution was insufficient to cause disease. Other factors, such as direct effects of Th1 cytokines on muscle tissue, may be involved in EAMG susceptibility.