Gamma-Terpinene Modulation of LPS-Stimulated Macrophages is Dependent on the PGE2/IL-10 Axis

Planta Med. 2016 Oct;82(15):1341-1345. doi: 10.1055/s-0042-107799. Epub 2016 May 25.

Abstract

Gamma-terpinene is a monoterpene present in the essential oils of several plants, including those from the Eucalyptus genus. This molecule was recently described as anti-inflammatory and microbiocidal, but little is known about the mechanisms behind its effects. The aim of the present study was to investigate the effect of gamma-terpinene on the lipopolysaccharide-induced production of cytokines by murine peritoneal macrophages. Gamma-terpinene treatment was found to reduce the production of proinflammatory cytokines, such as interleukin-1β and interleukin-6, and enhance that of the anti-inflammatory cytokine interleukin-10. This was accompanied by increased levels of the enzyme cycloxygenase-2 and its product, the lipid mediator prostaglandin E2. Inhibition of cycloxygenase-2 with nimesulide abolished the potentiating effect of gamma-terpinene on interleukin-10 production. Moreover, nimesulide treatment also abrogated the inhibitory effect of gamma-terpinene on interleukin-1β and interleukin-6. Furthermore, in macrophages from mice deficient in the interleukin-10 gene, gamma-terpinene failed to inhibit interleukin-1β and interleukin-6 production. These results suggest that this monoterpene promotes the prostaglandin E2/interleukin-10 axis, which inhibits the production of these proinflammatory cytokines.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclohexane Monoterpenes
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytokines / metabolism
  • Dinoprostone / metabolism*
  • Interleukin-10 / metabolism*
  • Interleukin-12 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice, Inbred BALB C
  • Monoterpenes / pharmacology*
  • Sulfonamides / pharmacology

Substances

  • Cyclohexane Monoterpenes
  • Cyclooxygenase Inhibitors
  • Cytokines
  • IL10 protein, mouse
  • Lipopolysaccharides
  • Monoterpenes
  • Sulfonamides
  • Interleukin-10
  • Interleukin-12
  • gamma-terpinene
  • Dinoprostone
  • nimesulide