ICAM-1-dependent pathway is not critically involved in the inflammatory process of autoimmune encephalomyelitis or in cytokine-induced inflammation of the central nervous system.

To determine whether the rat homolog of intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) we examined the effect of anti-ICAM-1 mAb, 1A29, on both active and passive EAE. We also examined its effect on a model of cytokine-induced inflammation in the central nervous system. Treatment of recipients of EAE effector cells with anti-ICAM-1 had no inhibitory activity, and in fact at high doses, treatment enhanced disease as evidenced by an earlier onset of symptoms. Treatment of active EAE with anti-ICAM-1 beginning on the day of sensitization did protect a proportion of animals from development of disease as well as reduce the severity of clinical signs in those which developed symptoms. Lymphocytes from both the draining lymph nodes and spleens of myelin basic protein (MBP)-immunized rats treated with anti-ICAM-1 failed to proliferate in response to MBP in vitro, suggesting that the antibody had prevented the animals from becoming sensitized to the antigen. Microinjection of tumor necrosis factor (TNF)-alpha into the spinal cords of rats led to the expression of ICAM-1 on vascular endothelium, and to the accumulation of leukocytes at sites of injection. The peak expression of ICAM-1 by endothelium and the peak accumulation of leukocytes following TNF alpha injection were not positively correlated. Furthermore, treatment of TNF alpha injected rats with anti-ICAM-1 did not inhibit the accumulation of leukocytes at the site of cytokine injection.(ABSTRACT TRUNCATED AT 250 WORDS)