Immunomodulation by polyaromatic hydrocarbons in mice and murine cells

Abstract

Several functionally defined in vitro antibody generating systems were used to assess the immunomodulating mechanisms of the benzopyrenes. When benzo(a)pyrene (BaP) or benzo(e)pyrene (BeP) was incorporated into a T-dependent antibody (TDAb)-producing spleen cell culture system, dose- and time-dependent inhibition of plaque-forming cell responses was observed. Addition of BaP at concentrations as low as 0.002 microgram/ml (7.93 nM) resulted in suppression of the TDAb plaque-forming cell response. BeP-induced suppression was seen at the 2-microgram level (7.93 microM). Time course evaluations demonstrated an early requirement for either chemical in culture in order to induce significant suppression. In vitro incorporation of BaP and BeP into polyclonal antibody-generating cultures also resulted in a dose-related inhibition. Inhibition of these antibody responses was also noted following in vivo exposure of mice to BaP or BeP. Fourteen-day exposure of mice to BaP (40 mg/kg) resulted in 98% suppression of the TDAb response. Polyclonal antibody responses were reduced 50 to 66% following 7 days of chemical exposure. BeP caused 51% suppression of the TDAb response following 14-day exposure of animals. These studies indicate that the suppressive effects of the benzopyrenes are multicellular in origin, occur apart from the carcinogenic effects of the chemicals, and cannot be attributed merely to cellular toxicity.