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

  • Zheng Z
  • Specter S
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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 α (TNF-α), 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-α protein and reduced TNF-α bioactivity in the culture supernatant. However, THC did not inhibit the levels of LPS-induced TNF-α mRNA and intracellular TNF-α precursor protein, had only a weak effect on expression of membrane-bound TNF-α, but suppressed TNF-α maturation/secretion by macrophages. The higher the THC concentration in the medium during TNF-α induction, the greater the amount of intracellular TNF-α precursors that accumulated in the activated macrophages and the less mature TNF-α was released from the cells. Data suggest that TNF-α production by macrophages was altered greatly by exposure to THC at the levels of TNF-α precursor maturation and secretion.

Author-supplied keywords

  • delta-9-tetrahydrocannabinol (THC)
  • macrophage
  • marijuana
  • tumor necrosis factor α

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Authors

  • Zhi Ming Zheng

  • Steven C. Specter

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