Experimental allergic encephalomyelitis. Inhibition of clinical signs and paradoxical enhancement of lesions in second attacks.

Experimental allergic encephalomyelitis (EAE) was induced in rats by immunization with neural antigens, with or without adjuvants. A second attack was induced after an interval of 3-24 weeks. When the second attack was produced by moderately intense active immunization or by passive transfer, the rats were protected from clinical signs. Paradoxically, the second attack regularly produced more lesions in the cerebellum than in naive contols. Inhibition of clinical signs and the accompanying paradoxical enhancement of cerebellar lesions were independent of the type of antigen or adjuvant used for either attack, the severity of the attacks, and the time interval between them. Nor did non-specific adrenal-mediated stress play any role in these phenomena. Even in the absence of clinical signs, the second attack produced many lesions in the spinal cord, but these were sometimes less severe than those produced in naive controls. The observation that an initial attack of EAE had different influences on susceptibility to a second attack in different parts of the nervous system is more readily explained by local tissue factors than by systemic regulatory influences.