AMELIORATION OF ANTIGEN-INDUCED ARTHRITIS IN RABBITS TREATED WITH MONOCLONAL-ANTIBODIES TO LEUKOCYTE ADHESION MOLECULES

Objective. To examine the effects of treatment of antigen-induced arthritis in rabbits with a monoclonal antibody against CD18, the common beta-chain of the leukocyte adhesion molecules. Intraarticular injection of antigen into primed rabbits elicits an acute inflammatory response followed by chronic arthritis in this model. Methods. Anti-CD18 was given at the time of intraarticular antigen administration, and effects on the acute and chronic arthritis were investigated. Twenty-four rabbits were examined (11 controls, 3 receiving normal mouse IgG, and 10 receiving anti-CD18). Results. Flow cytometry of blood leukocytes at anti-CD18 administration showed saturating amounts of mouse Ig coating all the circulating cells. Treatment effects on the acute arthritis (measured by quantiating the synovial cell exudate 24 hours after arthritis induction) were a profound reduction in the number of inflammatory cells and a striking decrease in the proportion of polymorphonuclear leukocytes recovered from the synovial cavity, indicating a decrease in acute inflammation. Treatment effects on the chronic synovitis (2 and 4 weeks later) compared with controls showed a significant decrease in synovial fluid cell counts at 2 weeks (1.7 versus 21.0 x 10(6)/joint, P < 0.03) and at 4 weeks (7.4 versus 22.6 x 10(6)/joint, P < 0.05). Histologic evaluation of the synovium (0-3+ scale, scored "blindly") of anti-CD18-treated rabbits and controls showed marked decreases in subsynovial cell infiltration and lymphoid follicle formation both at 2 weeks (1.0 versus 2.25, P < 0.005; and 0 versus 1.75, P < 0.001) and at 4 weeks (1.48 versus 2.17, P < 0.01; and 0.75 versus 2.08, P < 0.02). Quantitation of cartilage-bound immune complexes, and of synovial synthesis of Ig and specific antibody showed no differences between groups. Conclusion. These findings indicate that treatment with monoclonal antibody to CD18 not only modifies the initial acute arthritis, but also results in significant amelioration of the subsequent chronic inflammation in this animal model of rheumatoid arthritis.