Immunosuppressive effects of highly chlorinated biphenyls and diphenyl ethers on T-cell dependent and independent...

The dose-dependent effects of 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (nonaCB), 2,2',3,3',4,4',5,6,6'-nonaCB, 2,2',3,3',4,5,5',6,6'-nonaCB and decaCB on the suppression of the splenic plaque-forming cell (PFC) response to the T-cell-dependent antigen, sheep red blood cells (SRBCs) and the T-cell-independent antigen, trinitrophenyl-lipopolysaccharide (TNP-LPS), were determined in genetically inbred mice. In addition, the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was also measured. The highly chlorinated biphenyls suppressed the splenic PFC response to SRBCs in C57BL/6 and DBA/2 mice and were relatively more active in the former strain. The C57BL/6 mice are more responsive to aryl hydrocarbon (Ah) receptor agonists than DBA/2 mice and these data support a possible role for the Ah receptor in mediating this response. However, previous studies with polychlorinated biphenyls (PCBs) indicate that congeners with 3 or 4 ortho-chloro substituents are inactive as Ah receptor agonists and this was consistent with the minimal induction of hepatic microsomal EROD activity by the highly chlorinated biphenyls in both strains of mice. Thus, the results suggest that the inhibition of the splenic PFC response to SRBCs observed in this study was primarily an Ah receptor-independent response. Some of the highly chlorinated diphyenyl ethers namely decachlorodiphenyl ether and 2,2',3,3',4,4',5,6,6'-nonachlorodiphenyl ether, inhibited the antigenic response to TNP-LPS in C57 BL/6 mice. The results indicate that the suppression of the TNP-LPS-mediated immune response may be a more reliable indicator of the Ah receptor-dependent immunotoxicity of halogenated hydrocarbons.