Pathogenesis and treatment of chronic arthritis

Inflammatory and 'non-inflammatory' forms of arthritis affect a large proportion of the population and these diseases can often lead to disability. Although the pain of arthritis can be relieved to some extent by the peripherally acting aspirin-like drugs, the progression of disease leading to joint destruction is largely resistant to current drug therapy. The synovial joints of patients with rheumatoid arthritis are infiltrated with neutrophils, macrophages and lymphocytes and the resident cells become activated to degrade the cartilage and bone. The inflammatory and destructive changes that occur are brought about by the action of mediators or local hormones which are produced by a variety of cell-types. Lipid mediators, such as prostaglandins, contribute to the symptoms of arthritis while polypeptide cytokines, such as interleukin 1 and tumour necrosis factor, play a key role in joint destruction by activating the synovial cells and chondrocytes to release metalloproteinases, such as collagenase. Aspirin-like drugs inhibit the production of prostaglandins from inflamed tissues and thereby blunt the symptoms of arthritis. However, these drugs do not suppress the production of collagenase from connective tissue cells and, therefore, do not halt the degeneration of joint tissues.