Disruption of the IL-1β gene diminishes acetylcholine receptor-induced immune responses in a murine model of myasthenia gravis

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