Abstract

The inflammatory cytokine cascade plays a pivotal role in the pathogenesis of rheumatoid arthritis. Recently, a novel human cytokine, interleukin-32, was reported to induce tumor necrosis factor (TNF)-alpha. Interleukin-32 is expressed primarily in lymphoid tissues and leukocytes, but also in stimulated epithelial cells and synovial fibroblasts. Although the interleukin-32 receptor has not been reported, interleukin-32 can induce other inflammatory cytokines such as TNF-alpha, interleukin-1beta, and interleukin-6 from monocytes/macrophages in vitro and in vivo, and it synergizes with signals from pattern-recognition receptors. Notably, in the inflamed synovial tissues from rheumatoid arthritis patients, interleukin-32 is prominently expressed and correlates with the severity of arthritis and the expression of other cytokines, including TNF-alpha and interleukin-1. In experimental mice models of arthritis, joint injection of interleukin-32 induces joint inflammation, and overexpression of interleukin-32beta in hematopoietic cells exacerbates collagen-induced arthritis. Interleukin-32 can thus be seen to play an important role in the pathogenesis of rheumatoid arthritis.