Pertussis toxin-induced hyperacute autoimmune encephalomyelitis in Lewis rats is correlated with increased expression of inducible nitric oxide synthase and tumor necrosis factor alpha

The involvement of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha), which have diverse roles in the progression of autoimmune disease models, was studied in pertussis toxin (PT)-induced hyperacute experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The expression of TNF-alpha mRNA (increased 5-fold, P < 0.01) and iNOS protein (3-fold, P < 0.01) was much greater in the spinal cords with PT(+) EAE at the peak stage of EAE than in those with PT(-) EAE, as shown by competitive PCR and Western blot analysis, respectively. Immunohistochemistry showed that the majority of ED1-positive macrophages in EAE lesions contained iNOS, and that there were many more iNOS-positive cells in the CNS lesions of PT(+) rats than in those of PT(-) rats. These findings suggest that PT-induced hyperacute EAE is partly mediated by the enhanced expression of iNOS and TNF-alpha in the early stages of rat EAE. (C) 2001 Published by Elsevier Science Ireland Ltd.