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 μM) 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 PPARγ, its anti IL-6 effects are PPARγ independent. These studies provide evidence to support the view that AjA may prove to be an effective, safe antiinflammatory agent.