Evaluation of immunomodulatory chemicals: alteration of macrophage function in vitro

In an effort to develop a useful screening procedure for detecting potential modulators of macrophage function, 25 chemicals were tested for their ability to alter the nonspecific phagocytosis and killing of Saccharomyces cerevisiae by elicited mouse peritoneal macrophages (PM). Parallel studies monitored PM viability so as to distinguish between effective modulation of phagocytic function and changes due solely to cytotoxicity. Dextran sulfate, iota-carrageenan, lambda-carrageenan, dipropyltin dichloride, and di-n-octyltin dichloride, at concentrations which did not produce overt toxicity, significantly reduced the percentage of PM capable of ingesting yeast. The carrageenans also decreased the average number of yeast ingested per PM, while increasing the ability of PM to kill yeast. Microbicidal activity was suppressed in PM treated with indomethacin and dextran sulfate. Di-n-octyltin dichloride and dextran sulfate diminished the adherence of PM, whereas levamisole enhanced PM adherence. Vanillin, propyl gallate, lead acetate, hydrocortisone 21-phosphate, and hydrocortisone 21-hemisuccinate decreased the percentage of PM capable of ingesting yeast, but not below 50% of the control. Gallic acid, methyl paraben, mercuric chloride, cadmium chloride, nickel chloride, chromic chloride, dimethyltin dichloride, diethyltin dichloride, dibutyltin dichloride, tetra-n-octyltin, gibberellic acid, cyclophosphamide, and azathioprine did not alter PM phagocytic function at noncytotoxic doses. The results indicate that chemicals can be grouped into three broad categories as either ineffective, weak modulators, or effective modulators of PM function.