Effects of CI-949, a novel antiallergy agent, on immune function of male Fischer 344 rats

MR Bleavins, FA de la Iglesia, AE Munson, JA McCay, ML Stern, BA Fuchs and KL White

Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan.

CI-949 is an orally effective inhibitor of allergic mediator release as measured with in vitro and animal models. To assess the effects of CI- 949 on immune function, male Fischer 344 rats were evaluated for splenic T- and B-lymphocyte populations, antibody-forming cell response to sheep red blood cells (sRBC), concanavalin A- and pokeweed mitogen- induced lymphocyte proliferation, Natural Killer cell activity and reticuloendothelial system clearance of sRBC. CI-949 was administered by gavage to rats at 25, 50 and 100 mg/kg/day for 14 consecutive days. A vehicle control and two positive controls (cyclosporine A and cyclophosphamide) were run concurrently. CI-949 at 100 mg/kg/day decreased body weight gain and was lethal to 5 of 40 rats. The deaths occurred between days 5 and 12 of study. This overtly toxic dose did not alter splenic cellularity or change the percentages of T- and B- lymphocyte subpopulations. Additionally, CI-949 did not inhibit lymphocyte proliferation or hinder clearance of sRBC by the reticuloendothelial system. Antibody-forming cell response after immunization showed a dose-related increase in the number of immunoglobulin M secreting cells. Based on the results of these assays, the immune system does not appear to be adversely affected by CI-949 even at high doses.

Volume 257, Issue 1, pp. 316-322, 04/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics