Central administration of perfluorooctanoic acid inhibits cutaneous inflammation

To elucidate the site of action of perfluorooctanoic acid (PFOA) in the carrageenan model of peripheral inflammation.

Male Sprague-Dawley rats.

We first compared the anti-edema effects of systemic PFOA (50-150 mg/kg) with prototypical nonsteroidal (acetylsalicylic acid, ASA, 50-200 mg/kg) and steroidal (dexamethasone, 0.5-5.0 mg/kg) drugs after the intraplantar injection of carrageenan (1%). We then compared the anti-edema effects of systemic PFOA with local intraplantar (10 mg/kg), and intracerebroventricular (i.c.v., 0.1-50 mug) routes of administration.

Systemic PFOA was at least as or more efficacious than ASA or dexamethasone in reducing carrageenan-induced edema. RU-486 did not change the anti-edema effect of PFOA, ruling out a contribution of endogenous release of glucorticoids. I. c. v. PFOA, but not perfluorooctanes, dramatically reduced multiple signs of inflammation at doses well below the systemically-effective dose. We conclude that the anti-edema effect of high systemic doses of PFOA (> or =100 mg/kg, i. p.) is mediated in part by actions in the brain.