Linomide, a synthetic
immunomodulator, increases natural killer (NK) activity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the autoimmune manifestations of lupus-like disease in MRL/lpr mice and the clinical and pathological signs of acute and chronic-relapsing
experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined the effect of
linomide (100 mg/kg/day; administered in
drinking water) on rabbits and rats with
experimental autoimmune myasthenia gravis (EAMG). 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 stimulation. In contrast, mild signs of weakness appeared in only two of five
linomide-treated rabbits, with EMG borderline positive in one of them. Booster immunization with Torpedo AChR induced severe relapse and death in two EAMG control rabbits, whereas the two
linomide-treated animals remained free of myasthenic symptoms. The serum level of
antibodies 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 proliferative response of lymph node cells to Torpedo AChR and the purified
protein derivative of Mycobacterium tuberculosis was significantly lower in the
linomide-treated EAMG rats than in the controls.
Linomide may constitute a new immunomodulating agent for the treatment of
myasthenia gravis.