Inhibition of interleukin-2 production and lymphocyte responsiveness by the cell activation inhibitor, CI-959. |
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Authors: | M K Dong D J Wilburn M C Conroy R B Gilbertsen |
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Institution: | Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105. |
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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. |
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