Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator, perfluorooctanoic acid

In a previous investigation, we demonstrated that severe thymus and spleen atrophy occurs in mice upon dietary exposure to several potent peroxisome proliferators (PI's). In the present investigation, the effects of the potent PP perfluorooctanoic acid (PFOA) on the adaptive immunity of mice was evaluated both in vivo and ex vivo. The in vivo immune response examined involved immunization of mice with horse red blood cells (HRBCs), displaying T-cell-dependent antigens after pre-treatment with a PFOA-containing diet for 10 days. Subsequent quantitation of the primary Immoral response was performed employing both the plaque-forming cell (PFC) assay and determination of the antibody titer by ELISA. The results clearly demonstrate that oral administration of PFOA prevents both the increases in plaque formations by anti-IgM and -IgG and in serum levels of IgM and IgG normally evoked by such immunization. Ex vivo spleen cells proliferation (assayed as incorporation of H-3-thymidine) in response to both T- and B-cell activators was attenuated by dietary treatment with PFOA, although the analogous in vitro treatment of mouse spleen cells with this same compound had no such effects. Thus, the relatively metabolically inert PP PFOA may exert adaptive immunosuppression in mice by an indirect mechanism. The possible relevance of this immunosuppression to the alterations in plasma lipids caused by PPs is discussed. (C) 2002 Elsevier Science B.V. All rights reserved.