Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines

Int Immunopharmacol. 2015 May;26(1):257-64. doi: 10.1016/j.intimp.2015.03.034. Epub 2015 Apr 6.


Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree by removing up to 99% of the more toxic, hydrophobic monoterpenes. MAC was examined here for its immunomodulatory effects on the human THP1 and murine RAW264.7 myeloid leukemic cell lines as models for macrophage-like cells. Firstly, MAC levels were determined that did not affect either the survival or proliferation of these cell lines in vitro. Next, the levels of lipopolysaccharide (LPS)-induced production of cytokines (IL-6, TNFα, IL-10, GM-CSF, IFNγ and IL-3) were examined from the myeloid cell lines using multiplex assays. Many of the LPS-inducible cytokines produced by either cell lines could be significantly inhibited by MAC. Closer examination of the mechanism of action of MAC showed that it inhibited the LPS-induced activation of IκB phosphorylation and nuclear factor (NF)-κB signalling and translocation, inhibiting iNOS protein expression and NO production. These results demonstrate that MAC exerts its immunomodulatory effects by inhibiting NF-κB signalling activation and levels of cytokine production by macrophage-like cell lines.

Keywords: Cytokines; Immunomodulation; Melaleuca alternifolia concentrate (MAC); Myeloid cells; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression / drug effects
  • Humans
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / toxicity
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Melaleuca / chemistry*
  • Mice
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • Tea Tree Oil / chemistry*


  • Cytokines
  • Immunologic Factors
  • Lipopolysaccharides
  • NF-kappa B
  • Tea Tree Oil