TREATMENT OF CHRONIC-RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS WITH THE SYNTHETIC IMMUNOMODULATOR LINOMIDE (QUINOLINE-3-CARBOXAMIDE)

Linomide is a synthetic immunomodulator that enhances natural killer c ell activity and significantly activates several lymphocytic cell subp opulations in both experimental animals and humans. In this study we e xamined the effect of linomide (80 mg per kg per day in drinking water ) on mice with chronic-relapsing experimental autoimmune encephalomyel itis (CR-EAE), a T-cell-mediated organ-specific autoimmune disease tha t resembles human multiple sclerosis. None of the mice (n = 17) that w ere treated with linomide from day 7 after disease induction developed any dinical or histopathological signs of CR-EAE, as compared to 19 o f 20 untreated controls that were severely paralyzed and had extensive demyelinating lesions in the central nervous system. Linomide-treated animals were also resistant to an induced attack by a booster injecti on with a murine spinal cord homogenate. When administered to mice exh ibiting severe clinical signs of paralysis, linomide inhibited both sp ontaneous and induced relapses. Linomide treatment protected mice from passively induced CR-EAE as well, when given from the day of injectio n with myelin-basic-protein-specific lymphocytes. Lymphocytes obtained from linomide-treated mice had a reduced in vitro proliferative respo nse to the myelin basic protein and to the tuberculin purified protein derivative, whereas the mitogenic response to concanavalin A was not affected. Natural killer cell and lymphokine-activated killer cell act ivities were enhanced. These results suggest that linomide regulates a utoimmunity in the absence of systemic immunosuppression. Since linomi de is very well tolerated in experimental animals and humans, it might be used in the treatment of multiple sclerosis.