Effects of CI-949, a novel antiallergy agent, on immune function of male Fischer 344 rats.
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.
Bleavins
M R
MR
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan.
de la Iglesia
F A
FA
Munson
A E
AE
McCay
J A
JA
Stern
M L
ML
Fuchs
B A
BA
White
K L
KL
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D006633:Histamine Antagonists / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D007211:Indoles / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000187:drug effects; D013777:Tetrazoles / Q000633:toxicity*
D003524:Cyclosporins; D006633:Histamine Antagonists; D007211:Indoles; D013777:Tetrazoles; C061320:CI 949; D003520:Cyclophosphamide