Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages

Inflamm Res. 2014 Sep;63(9):769-78. doi: 10.1007/s00011-014-0749-x. Epub 2014 Jun 20.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cyclohexane Monoterpenes
  • Cyclohexenes / pharmacology*
  • Cytokines / immunology*
  • Humans
  • Lipopolysaccharides
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mitogen-Activated Protein Kinases / immunology
  • Monoterpenes / pharmacology*
  • NF-kappa B / immunology
  • Signal Transduction
  • Tea Tree Oil / pharmacology*
  • Terpenes / pharmacology*
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / immunology
  • U937 Cells


  • Anti-Inflammatory Agents
  • Cyclohexane Monoterpenes
  • Cyclohexenes
  • Cytokines
  • Lipopolysaccharides
  • Monoterpenes
  • NF-kappa B
  • TLR2 protein, human
  • TLR4 protein, human
  • Terpenes
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • alpha-terpineol
  • terpinenol-4
  • Tea Tree Oil
  • Mitogen-Activated Protein Kinases