title: Delta-9-tetrahydrocannabinol suppresses tumor necrosis factor alpha maturation and secretion but not its transcription in mouse macrophages.
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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612, USA.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Zheng
authors.forename: S C
authors.initials: SC
authors.lastname: Specter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D013759:Dronabinol / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013759:Dronabinol