INTERLEUKIN-1 RECEPTOR ANTAGONIST SUPPRESSES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) IN RATS BY INFLUENCING THE ACTIVATION AND PROLIFERATION OF ENCEPHALITOGENIC CELLS

Considering the role of pleiotropic interleukin-1 (IL-1) in inflammati on and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although t he role of CD4(+) T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated , the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. W e have evaluated the effect of human recombinant interleukin-1 recepto r antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 mu g/rat/day) developed milder signs of EAE, when compared to saline-trea ted control animals immunized with encephalitogen, which developed sev ere single episode disease. The transfer of lymph node cells (LNC) iso lated from MBP-primed DA rats and stimulated in vitro with MBP and Con A to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 mu g/ml) developed significant ly milder disease. Diminished encephalitogenic capacity of LNC correla ted with lower proliferative response to antigen and mitogen and decre ased expression of IL-2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lym phocytes. (C) 1998 Elsevier Science B.V. All rights reserved.