Disruption of the IL-1 beta gene diminishes acetylcholine receptor-inducedimmune responses in a murine model of myasthenia gravis

Human autoimmune myasthenia gravis (MG) is associated with the IL-1 beta Ta qI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1 beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine rece ptor (AChR) immunization in wild-type and IL-1 beta deficient ((-/-)) mice. Compared with wild-type mice, IL-1 beta (-/-) mice were relatively resista nt to induction of clinical experimental autoimmune myasthenia gravis (EAMG ). Draining lymph node cells from IL-1 beta (-/-) mice showed poor prolifer ative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) a nd Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1 beta (-/-) mice compared to wild-type mice. T aken together, these results reveal a critical role for IL-1 beta in the in duction of MG in mice, and support a role for IL-1 beta in the pathogenesis of MG in man.