The pathogenesis of rheumatoid arthritis: Pivotal cytokines involved in bone degradation and imflammation

Abstract

Proinflammatory cytokines, notably interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-γ), play an important role in initiating and perpetuating inflammatory and destructive processes in the rheumatoid joint. These cytokines regulate many nuclear factor κB inducible genes that control expression of other cytokines, cell adhesion molecules, immunoregulatory molecules, and proin-flammatory mediators. The expression of cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) and thereby production of prostaglandins (PG) and NO are regulated by cytokines. PGE2 and NO further promote inflammation and likely participate in destructive mechanisms in the rheumatoid joint. In some experimental systems, the effects of IL-1 and TFN-α appear synergistic, and correspondingly, concomitant inhibition of both cytokines provides greater than additive antiarthritic effects. Although the actions of IL-1 and TFN-α show a large degree of overlap, some differences have been observed in animal models. However, in patients with active rheumatoid arthritis, blockade of either cytokine results in clinical improvement and less radiographic progression.