The Relationship Between Noncoplanar PCB-Induced Immunotoxicity and Hepatic CYP1A Induction in a Fish Model

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Abstract
Abundant literature exists demonstrating the immunomodulating effects of polychlorinated biphenyls (PCBs). To date, most of the research has focused on dioxin-like coplanar PCB congeners because of their high affinity for the aryl hydrocarbon receptor (AhR) and cytochrome P450-inducing capability. For this study, the impact of two structurally different PCB congeners on the immune responsiveness of bluegill sunfish (Lepomis macrochirus) was examined to evaluate the immunotoxic potential of each congener (as separate entities) and to relate effects on immune function with hepatic CYP1A induction. Fish received a single intraperitoneal injection of the: coplanar congener, PCB 126 (0.01 or 1.0 μg/g BW); noncoplanar PCB 153 (5.0 or 50.0 μg/g BW); or, the corn oil vehicle. PCB-induced effects on innate and cell-mediated immune parameters, and on hepatic CYP1A protein induction were evaluated in fish sacrificed 1, 3, 7, 14 or 21 days post-injection. In the absence of CYP1A induction, PCB 153 increased kidney phagocyte-mediated superoxide production 3 d post-injection, and at the highest dose suppressed B- and T-lymphocyte proliferation after 3 and 7 days, respectively. Treatment of fish with PCB 126 had no effect on oxyradical production, but altered B-lymphocyte proliferation after 1 day, also in the absence of CYP1A induction. Hepatic CYP1A was only induced in fish exposed to the highest PCB 126 dose; protein induction appeared at 3 d post-injection and persisted for up to 21 days. Taken together, these results demonstrate that exposure to different PCB congeners can alter immune function in the absence of CYP1A induction, suggesting that mechanisms other than the AhR pathway may play a role in PCB-induced immunotoxicity, particularly for the noncoplanar congeners.

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