Exposure to the immunosuppressant, perfluorooctanoic acid, enhances the murine IgE and airway hyperreactivity response to ovalbumin.
These studies were conducted to investigate the role of dermal exposure to perfluorooctanoic acid (PFOA), a known immunosuppressant, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. PFOA has had widespread use as a carpet and fabric protectant. BALB/c mice were exposed dermally, on the dorsal surface of each ear, to concentrations of PFOA ranging from 0.01 to 1.5% (applied dose 0.25-50 mg/kg) for 4 days. In hypersensitivity studies, mice were also ip injected with 7.5 microg OVA and 2 mg alum on days 1 and 10 and in some studies challenged with 250 microg OVA by pharyngeal aspiration on days 17 and 26. Following exposure to PFOA, an increase in liver weights and a decrease in thymus and spleen weights and cellularities were observed. Similar immunomodulatory trends were demonstrated in mice coadministered PFOA and OVA. Compared to the OVA alone-exposed animals, an increase in total IgE was demonstrated when mice were coexposed to OVA and concentrations of PFOA ranging from 0.75 to 1.5%, while the OVA-specific IgE response peaked with 0.75% PFOA coexposure (p < or = 0.05). OVA-specific airway hyperreactivity was increased in the 1.0% PFOA coexposed group (p < or = 0.05), with an increased pleiotropic cell response characterized by eosinophilia and mucin production, in animals coexposed to concentrations of PFOA up to 1.0%, as compared to the OVA alone-exposed animals. In a murine model, PFOA was demonstrated to be immunotoxic following dermal exposure, with an enhancement of the hypersensitivity response to OVA, suggesting that PFOA exposure may augment the IgE response to environmental allergens.
Fairley
Kimberly J
KJ
National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Purdy
Rich
R
Kearns
Shaun
S
Anderson
Stacey E
SE
Meade
B  J
B
D000287:Administration, Topical; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D002210:Caprylates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D006967:Hypersensitivity / Q000503:physiopathology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology*; D010641:Phenotype; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology
D000941:Antigens; D002210:Caprylates; D005466:Fluorocarbons; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D010047:Ovalbumin; C023036:perfluorooctanoic acid