Wiemann B, Van G Y, Danilenko D M, Yan Q, Matheson C, Munyakazi L, Ogenstad S, Starnes C O
Department of Pharmacology, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
Exp Neurol. 1998 Feb;149(2):455-63. doi: 10.1006/exnr.1997.6723.
Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-alpha) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-alpha and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.
