Tumour necrosis factor α stimulates resorption and inhibits synthesis of proteoglycan in cartilage

Abstract

During inflammatory reactions, activated leukocytes are thought to produce a variety of small proteins (cytokines) that influence the behaviour of other cells (including other leukocytes). Of these substances, which include the interleukins, interferons and tumour necrosis factors (TNFs), interleukin-1 (IL-1) has been considered potentially a most important inflammatory mediator because of its wide range of effects (reviewed in refs 1, 2). In vivo it is pyrogenic and promotes the acute phase response; in vitro it activates lymphocytes³ and stimulates resorption of cartilage⁴ and bone^5,6. Cartilage resorption is a major feature of inflammatory diseases such as rheumatoid arthritis, and IL-1 is the only cytokine hitherto known to promote it. TNFs are characterized by their effects on tumours and cytotoxicity to transformed cells^7–9, but share some actions with IL-1.1 report here that recombinant human TNFα stimulates resorption and inhibits synthesis of proteoglycan in explants of cartilage. Its action is similar to and additive with IL-1, and it is a second macrophage-derived cytokine whose production in rheumatoid arthritis, or inflammation generally, could contribute to tissue destruction.