Delta-9-tetrahydrocannabinol suppresses tumor necrosis factor alpha maturation and secretion but not its transcription in mouse macrophages

Int J Immunopharmacol. 1996 Jan;18(1):53-68. doi: 10.1016/0192-0561(95)00107-7.

Abstract

Various in vitro studies have shown that delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has a variety of inhibitory effects on immune functions including effects on macrophages. The present studies have examined the mechanism of THC's effects on tumor necrosis factor alpha (TNF-alpha), a major macrophage-produced cytokine and an important mediator involved in cytokine networks and in host defense mechanisms. Exposure of macrophages to medium containing THC has resulted in low levels of soluble TNF-alpha protein and reduced TNF-alpha bioactivity in the culture supernatant. However, THC did not inhibit the levels of LPS-induced TNF-alpha mRNA and intracellular TNF-alpha precursor protein, had only a weak effect on expression of membrane-bound TNF-alpha, but suppressed TNF-alpha maturation/secretion by macrophages. The higher the THC concentration in the medium during TNF-alpha induction, the greater the amount of intracellular TNF-alpha precursors that accumulated in the activated macrophages and the less mature TNF-alpha was released from the cells. Data suggest that TNF-alpha production by macrophages was altered greatly by exposure to THC at the levels of TNF-alpha precursor maturation and secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dronabinol / pharmacology*
  • Immunosuppressive Agents / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / analysis
  • Transcription, Genetic / drug effects*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Immunosuppressive Agents
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Dronabinol