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Supression of humoral immunity by perfluorooctanic acid is independent of elevated serum corticosterone concentration in mice
Citation:
DEWITT, J., C. B. COPELAND, AND R. W. LUEBKE. Supression of humoral immunity by perfluorooctanic acid is independent of elevated serum corticosterone concentration in mice. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 109(1):106-112, (2009).
Impact/Purpose:
At higher doses of PFOA, immunosuppression is accompanied by loss of body weight and elevated corticosterone concentrations (a primary marker of stress), leading one recent publication to conclude that the changes in immune function they had also observed was a manifestation of stress, rather than authentic immunotoxicity. In other words, from a risk assessment standpoint, they concluded that effects of PFOA on immune function should be dismissed. To address the potential role of corticosterone in PFOA-induced suppression, adrenalectomized (adx) and sham-operated C57BLl6N female mice were exposed to PFOA and immunized to stimulate an antibody response.
Description:
The T-cell-dependent antibody response is suppressed in mice exposed to 3.75, 7.5, 15, and 30 mg PFOA (perfluorooctanoic acid)/kg body weight (bw). Reduced bw accompanied immunosuppression at 15 and 30 mg/kg. We investigated the hypothesis that the observed immunosuppression is secondary to elevated serum corticosterone levels by assessing immune function in adrenalectomized (adx) or sham-operated C57BL/6N female mice exposed to 0, 7.5, or 15 mg PFOA/kg bw in drinking water for 10 days. Bw, primary antibody responses to a T-dependent antigen, clinical serum chemistries related to liver health, and serum corticosterone levels were evaluated. Exposure to 15 mg/kg decreased bw by approximately 10% after 8 days of dosing and until 2 days postdosing in both adx and sham animals; bw of adx animals were still reduced 5 days postdosing. IgM antibody titers were statistically reduced by 15% in sham animals and 18% in adx animals exposed to 15 mg/kg and by 11.8% in adx animals exposed to 7.5 mg/kg. Corticosterone concentrations were elevated by 157% in dosed sham animals relative to control animals and were reduced by 27% in dosed adx animals relative to control animals (neither changes were statistically significant). Clinical serum chemistries related to liver health were not statistically altered by either dose or adrenalectomy. The failure of adrenalectomy to protect mice from the immunosuppressive effects of PFOA indicates that suppression of antibody synthesis is not the result of liver toxicity or stress-related corticosterone production.
