Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid.
Interleukin-6 (IL-6) is a multifunctional cytokine which contributes to inflammation and tissue injury in several diseases. Thus, inhibition of IL-6 production may be a useful strategy for treatment of patients with diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A synthetic nonpsychoactive cannabinoid, ajulemic acid (AjA), prevents joint damage in experimental arthritis. Results of experiments presented here indicate that addition of AjA (3-30 microM) to human monocyte derived macrophages in vitro reduces steady state levels of IL-6 mRNA and the subsequent secretion of IL-6 from LPS stimulated cells. Although AjA binds to and activates PPARgamma, its anti IL-6 effects are PPARgamma independent. These studies provide evidence to support the view that AjA may prove to be an effective, safe antiinflammatory agent.
Department of Medicine, Division of Rheumatology, University of Massachusetts Medical School, 55 Lake Ave, Worcester, MA 01655, USA.
Jennifer
J
Parker
Francisco
F
Atez
Ronald G
RG
Rossetti
Ann
A
Skulas
Rakesh
R
Patel
Robert B
RB
Zurier
D000813:Anilides / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D000813:Anilides; D013759:Dronabinol; D015850:Interleukin-6; D047495:PPAR gamma; D000093242:Interleukin-6 Inhibitors; C457499:2-chloro-5-nitrobenzanilide; C471849:lenabasum