Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders

G.      Munuswamy-Ramanujam; K.   A.   Khan; A.   R.   Lucas

Abstract

Inflammatory and immune responses are inherent in the development of progressive arthritic or vasculitic disorders. Arthritis is frequently associated with accelerated forms of vasculitis; atherosclerosis being one form of accelerated vasculitis that blocks blood flow causing heart attacks and strokes. The arterial supply is central to maintaining normal articular function and acts as a conduit for inflammatory (innate) and immune (antigen dependent) cell trafficking in joints. The vasculature in some cases can become inflamed in the disease process. While treatment of severely debilitating arthritic disorders has improved, some current treatments are limited to reducing symptoms while others act as disease modifying drugs (DMARDs), but may have limited success. Many current treatments also have reported adverse side effects. Vasculitic disorders are similarly debilitating with high associated morbidity and mortality and current therapy for these disorders is only partially successful. Immune-modifying agents, which alter vascular inflammation, thus have potential for application in rheumatologic diseases. Viral immune modulating proteins reduce early arterial inflammatory responses with associated reductions in atherosclerotic plaque development and transplant rejection in a wide range of animal models. A clinical trial utilizing one such viral reagent, a secreted myxomaviral serpin, is currently in progress, assessing treatment of acute coronary syndrome, a vascular syndrome with marked up-regulation of systemic inflammatory responses. In this review we examine viral antiinflammatory proteins as potential therapeutic reagents for arthritic and vasculopathic disorders.

Keywords: Rheumatic disease, arthritis, atherosclerosis, vasculitis, virus, chemokines, cytokine mimics, serpins, apoptosis