Use of staphylococcal enterotoxin A-induced lymphoproliferation and interleukin 2 production as indicators of immunotoxicity

Suppression of mitogen-induced splenocyte lymphoproliferation and interleukin 2 (IL-2) production can be used as indicators of immunotoxicity. Staphylococcal enterotoxin A (SEA) is both a potent mitogen and the most potent in vitro inducer of IL-2 production that has been described. An in vitro system was used to measure impairment of SEA-induced lymphoproliferation and IL-2 production using splenocytes from female C57BL/6 mice dosed with either cyclosporin A (30 mg/kg/day, 14 days), benzene (220, 440, or 880 mg/kg/day, 14 days), or vehicle. Splenocytes were stimulated with either concanavalin A (con A) or SEA. Benzene- and cyclosporin A-treated mice demonstrated significant decreases in splenocyte proliferation. IL-2 production was determined by incubating splenocyte culture supernatants with IL-2 dependent cytotoxic T-cells (CTLL-2), pulsing with 3H-thymidine, and determining amount of incorporated label. Cell proliferation and IL-2 production were inhibited by both benzene and cyclosporin A, effects more clearly demonstrated using SEA than con A. SEA was a superior mitogen compared to con A in the assays evaluated here.