Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway.