Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10

Carvacrol, a phenolic monoterpene, has been reported to possess anti-inflammatory properties. However, the mechanisms involved in its pharmacological properties are currently not well understood. In the present study, the contribution of cytokine modulation to the anti-inflammatory effects of carvacrol was investigated in a classical inflammation model: the complete Freund's adjuvant (CFA)-induced paw inflammation in mice. The paw edema was measured using a plesthismometer. Paw tissue was removed 2 h after the inflammatory stimulus to determine the levels of prostaglandin E-2 (PGE(2)) by enzyme immunoassay, the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) by ELISA or the mRNA expression of cyclooxygenase-2 (COX-2), IL-1 beta, TNF-alpha, and IL-10 by real-time PCR. Administration of carvacrol produced anti-inflammatory effects against CFA-induced inflammation in mice. Treatment of mice with carvacrol at 50 and 100 mg/kg attenuated the paw edema and reduced the IL-1 beta and PGE(2), but not TNF-alpha, local levels. Similarly, carvacrol (100 mg/kg) reduced the COX-2 and IL-1 beta mRNA expression. The levels of IL-10, an anti-inflammatory cytokine, and the IL-10 mRNA expression in the inflamed paw were enhanced by carvacrol. In addition, the treatment with carvacrol did not reduce the CFA-induced paw edema in IL-10 knockout mice. The present results suggest that carvacrol causes anti-inflammatory effects by reducing the production of inflammatory mediators, such as IL-1 beta and prostanoids, possibly through the induction of IL-10 release. (C) 2012 Elsevier B.V. All rights reserved.