title: Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages.
abstract: OBJECTIVE
  Tea tree oil (TTO) is an essential oil with anti-inflammatory properties, steam distilled from the plant Melaleuca alternifolia. We investigated the immunomodulatory properties of TTO and its components (terpinen-4-ol and alpha-terpineol) using lipopolysaccharide (LPS)-stimulated macrophages.
  
  
  METHODS
  The ability of TTO, terpinen-4-ol and alpha-terpineol to modulate the macrophage response to bacterial LPS stimulation was assessed by ELISA for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 cytokine production and by western blotting for the activation of nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling, which are associated with the expression of pro-inflammatory cytokines. We used a human monocytic cell line (U937) differentiated into macrophages.
  
  
  RESULTS
  LPS induced the production of all cytokines, and TTO and its components significantly reduced the production of IL-1β, IL-6 and IL-10. The production of TNF-α was not affected by either TTO or its major components. The modulation of cytokine production was not mediated by changes in NF-κB or p38 MAPK activation.
  
  
  CONCLUSIONS
  TTO, terpinen-4-ol and alpha-terpineol can suppress the production of inflammatory mediators in LPS-stimulated human macrophages; this inhibition was mediated by interfering with the NF-kB, p38 or ERK MAPK pathways.
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry Araraquara, UNESP, Araraquara, SP, Brazil, nicolenogueira2@yahoo.com.br.
authors.forename: M N M
authors.initials: MN
authors.lastname: Nogueira
authors.forename: S G
authors.initials: SG
authors.lastname: Aquino
authors.forename: C
authors.initials: C
authors.lastname: Rossa Junior
authors.forename: D M P
authors.initials: DM
authors.lastname: Spolidorio
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000276:immunology; D015398:Signal Transduction; D020947:Tea Tree Oil / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D016207:Cytokines; D008070:Lipopolysaccharides; D039821:Monoterpenes; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013729:Terpenes; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C016775:alpha-terpineol; C034019:terpinenol-4; D020947:Tea Tree Oil; D020928:Mitogen-Activated Protein Kinases