Inhibition of interleukin-2 production and lymphocyte responsiveness by the cell activation inhibitor, CI-959.
CI-959 (5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo [b]-thiophene-2-carboxamide), an antiallergy compound, blocked release of IL-2 from Con A stimulated rat splenocytes and human lymphocytes with respective IC50s of 19.1 and 23.1 microM. Inhibition of IL-2 production required the presence of CI-959 in culture medium for the first 9 hr. CI-959 also inhibited Con A-stimulated rat and human lymphocyte proliferation with IC50s of 4.7 and 5.4 microM, respectively. Inhibition of the Con A proliferative response could not be overcome by exogenous recombinant human IL-2 (300 units/ml) in either the rat or human systems. Although potent in the human mixed lymphocyte reaction (IC50 = 3.5 microM), CI-959 was less effective in blocking the PHA response (IC50 = 43.9 microM), and had minimal effect on the release of IL-1 and TNF alpha from LPS-stimulated human monocytes. These findings suggest that CI-959 selectively inhibits some lymphocyte functions, as opposed to monocyte functions, and that among these is the production of IL-2.
Dong
M K
MK
Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105.
Wilburn
D J
DJ
Conroy
M C
MC
Gilbertsen
R B
RB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003864:Depression, Chemical; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects*; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010835:Phytohemagglutinins; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D013777:Tetrazoles; D013876:Thiophenes; D003208:Concanavalin A; C061662:CI 959