title: Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10.
abstract: 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 2h after the inflammatory stimulus to determine the levels of prostaglandin E(2) (PGE(2)) by enzyme immunoassay, the levels of interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) by ELISA or the mRNA expression of cyclooxygenase-2 (COX-2), IL-1β, TNF-α, 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 100mg/kg attenuated the paw edema and reduced the IL-1β and PGE(2), but not TNF-α, local levels. Similarly, carvacrol (100mg/kg) reduced the COX-2 and IL-1β 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-1β and prostanoids, possibly through the induction of IL-10 release.
authors.affiliation: Universidade Federal da Bahia, Barão de Jeremoabo s/n, CEP 40170-290, Salvador, Bahia, Brazil.
authors.forename: Milena da Silva
authors.initials: Mda S
authors.lastname: Lima
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.forename: Wagno Alcântara
authors.initials: WA
authors.lastname: de Santana
authors.forename: Carla
authors.initials: C
authors.lastname: Martins Kaneto
authors.forename: Milena Botelho
authors.initials: MB
authors.lastname: Pereira Soares
authors.forename: Cristiane Flora
authors.initials: CF
authors.lastname: Villarreal
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000081007:Cymenes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D000081007:Cymenes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D039821:Monoterpenes; D011453:Prostaglandins; D012333:RNA, Messenger; D016753:Interleukin-10; C073316:carvacrol