Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid
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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.
KeywordsInterleukin-6 Inflammation Cannabinoid acid Macrophages Rheumatoid arthritis
This study was supported by National Institute of Health Grants DA3691, AI1056362, and T32AR07572 (RP, Trainee), and a grant from the FAO Schwarz Research Foundation (FA, Trainee).
- 2.Abeles AM, Pillinger MH (2006) The role of synovial fibroblasts in rheumatoid arthritis-cartilage destruction and the regulation of matrix metalloproteinases. Bull Hosp Jt Dis 64:20–24Google Scholar
- 5.Dasgupta B, Corkill M, Kirkham B, Gibson T, Panayi G (2002) Serial estimation of interleukin-6 as a measure of systemic disease in rheumatoid arthritis. J Rheumatol 19:22–25Google Scholar
- 6.Choy EHS, Isenberg DA, Garrood T, Farrow S, Ioannou Y, Bird H, Cheung N, Williams B, Hazleman B, Price R, Yoshizaki K, Nishimoto N, Kishimoto T, Panayi GS (2002) Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis. A randomized double blind, placebo-controlled dose escalation trial. Arthritis Rheum 46:3143–3150PubMedCrossRefGoogle Scholar
- 7.Kaplin AI, Deshpande DM, Scott E, Krishnan C, Carmen JS, Shats I, Martinez T, Drummond J, Dike S, Pletnikov M, Keswani SC, Moran TH, Pardo CA, Calabresi PA, Kerr DA (2005) IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis. J Clin Invest 115:2731–2741PubMedCrossRefGoogle Scholar
- 9.Abel EL (1980) Marijuana: the first twelve thousand years. Plenum, New YorkGoogle Scholar
- 27.Fahmi H, Pelletier JP, Martel-Pelletier J (2003) PPAR gamma ligand as modulators of inflammatory and catabolic responses in arthritis: an overview. J Rheumatol 29:3–14Google Scholar