IMMUNOMODULATION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS WITH LINOMIDE

Linomide, a synthetic immunomodulator, increases natural killer (NK) a ctivity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the a utoimmune manifestations of lupus-like disease in MRL/lpr mice and the clinical and pathological signs of acute and chronic-relapsing experi mental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined t he effect of linomide (100 mg/kg/day; administered in drinking water) on rabbits and rats with experimental autoimmune myasthenia gravis (EA MG). Following immunization with Torpedo acetylcholine receptor (AChR) , all control rabbits developed clinical signs of severe weakness and exhibited a decrement of muscle action potential upon repetitive stimu lation. In contrast, mild signs of weakness appeared in only two of fi ve linomide-treated rabbits, with EMG borderline positive in one of th em. Booster immunization with Torpedo AChR induced severe relapse and death in two EAMG control rabbits, whereas the two linomide-treated an imals remained free of myasthenic symptoms. The serum level of antibod ies against both Torpedo and rat AChR were markedly suppressed in the linomide-treated animals. Similar inhibition of clinical signs of EAMG was observed in the EAMG rat model. Furthermore, the in vitro prolife rative response of lymph node cells to Torpedo AChR and the purified p rotein derivative of Mycobacterium tuberculosis was significantly lowe r in the linomide-treated EAMG rats than in the controls. Linomide may constitute a new immunomodulating agent for the treatment of myasthen ia gravis.