Polymyalgia versus giant cell arteritis

The role of myokines and nucleotides in vascular inflammation

Volker Nehls

Obliterative temporal arteritis, polymyalgia rheumatica and RS3PE-syndrom are recognized as different phenotypes of the same disease, i.e. giant cell arteritis. The incidence of ischemic complications decreases when systemic symptoms (muscle pain, fever, arthritis, anemia) develop. A novel concept for the pathogenesis of polymyalgia rheumatica is proposed postulating that muscle- derived molecules alleviate vascular inflammation in giant cell arteritis. ATP is released in large amounts from working or activated muscle cells. ATP stimulates P2X7 purinergic receptors on sensory fibers and causes muscle pain. Extracellular ATP is rapidly hydrolyzed by ectonucleotidase-enzymes, generating AMP and finally adenosine. Adenosine acts as a potent vasodilator and immunosuppressive molecule, suppressing TH1-immunity and interferon-gamma production by lymphocytes. Thus, adenosine appears ideally suited to prevent ischemic complications in giant cell arteritis. Other muscle-derived cytokines which are likely to participate in fighting arteritis and vessel occlusion may be interleukin-6 and VEGF. VEGF induces angiogenesis and collateral formation and increases capillary permeability, thereby leading to edematous swellings in RS3PE syndrome. The review discusses the hypothesis that polymyalgia is not the disease but possibly the reaction of the organism which tries to keep blood vessels patent by releasing vasoactive and immunomodulatory molecules from muscle cells and adipocytes. Alternatively, a primary defect in the generation of adenosine might facilitate inflammatory processes in arteries. It remains to be shown whether polymyalgia/giant cell arteritis is of autoimmune origin or, rather , a disorder of the purinergic system.

online since 2008/07/19

article in German