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-mu-M. 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-mu-M, 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-mu-M), CI-959 was less effective in blocking the PHA response (IC50 = 43.9-mu-M), 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.