THALIDOMIDE PROLONGS EXPERIMENTAL AUTOIMMUNE NEURITIS IN LEWIS RATS

Thalidomide is reported to have immunomodulatory and anti-inflammatory effects, which have led to its use in the treatment of a number of im mune-mediated disorders, including leprosy, discoid lupus and Behcet's disease, and to prevent immunological rejection phenomena following s kin and bone marrow grafts. Experimental autoimmune neuritis (EAN) is a CD4(+) T-cell-mediated demyelinating autoimmune disease, which repre sents an animal model for the study of the immunopathogenesis and immu notherapy of Guillain-Barre syndrome (GBS) in humans. We examined the effect of thalidomide in Lewis rats with EAN, which was induced by imm unization with bovine peripheral nerve myelin (BPM) and complete Freun d's adjuvant (CFA). Thalidomide prolonged clinical EAN when given at a dose of 200 mg/kg/day by gavage. This clinical effect was associated with increased numbers of inflammatory cells in sciatic nerve sections and elevated numbers of interferon-gamma (IFN-gamma) mRNA-expressing cells among lymph node mononuclear cells from thalidomide-treated EAN rats on day 17 postimmunization, i.e. at the peak of clinical EAN. The finding that thalidomide prolongs clinical EAN is in agreement with t he clinical polyneuropathy reported in patients receiving treatment wi th thalidomide and limits its clinical usefulness.