title: Inhibition of interleukin-2 production and lymphocyte responsiveness by the cell activation inhibitor, CI-959.
abstract: 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.
authors.affiliation: Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105.
authors.forename: M K
authors.initials: MK
authors.lastname: Dong
authors.forename: D J
authors.initials: DJ
authors.lastname: Wilburn
authors.forename: M C
authors.initials: MC
authors.lastname: Conroy
authors.forename: R B
authors.initials: RB
authors.lastname: Gilbertsen
mesh_terms: 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*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D013777:Tetrazoles; D013876:Thiophenes; D003208:Concanavalin A; C061662:CI 959