ToxSci Advance Access originally published online on February 23, 2009
Toxicological Sciences 2009 109(1):106-112; doi:10.1093/toxsci/kfp040
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Suppression of Humoral Immunity by Perfluorooctanoic Acid is Independent of Elevated Serum Corticosterone Concentration in Mice
* Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834
Immunotoxicology Branch, Experimental Toxicology Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709
1 To whom correspondence should be addressed at Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, 600 Moye Blvd., Greenville, NC 27834. Fax: (252) 744-3203. E-mail: dewittj{at}ecu.ecu.
Received December 5, 2008; accepted February 18, 2009
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Abstract |
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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.
Key Words: perfluoronated agents; immunotoxicity; corticosterone.