Screening for Immunomodulators: Effects of Xenobiotics on

Macrophage chemiluminescence (CL) was evaluated as a primary screening assay by assessing the modulatory activity of 17 different chemicals. The chemicals were either known immuno-modulatory drugs or environmental toxicants with reported immunomodulatory activity. Elicited mouse peritoneal macrophages were exposed to the chemicals in vitro, and CL was measured in response to an opsonized yeast stimulus. Ten chemicals (hydrocortisone, dextran sulfate, di-fl-octyltin dichloride, dimethyltin dichloride, azathioprine, lambda carrageenan (1-carrageenan), lead, A'-propyl gallate, gallic acid, and indomethacin) were identified as effective modulators of CL. The polyanions dextran sulfate and 1-carrageenan either suppressed or en-hanced CL, depending on the experimental conditions, while the remaining modulators were inhibitory. A series of secondary assays was used to verify this modulatory activity and to explore different mechanisms of action. Each effective modulator altered only a few specific components of the more complex CL response, and the following general mechanisms were apparent. At least 2 chemicals showed distinct antioxidant activity and thus probably did not alter functional aspects of macrophage CL. Chemicals which blocked Fc receptor function delayed the peak CL of macrophages stimulated by opsonized yeast. Nine of the 10 modulators inhibited hydroge