Udalova I., Monaco C., Nanchahal J., Feldmann M.
© 2017 American Society for Microbiology, Washington, DC. Tumor necrosis factor (TNF) is a member of the large family of cytokines; not hormones, but important local signaling molecules that transmit information from one cell to another (1). Different cytokines convey different messages, but cytokines are key players in every important biological process, including immunity, inflammation, cell growth, migration, fibrosis, vascularization, etc. So it is not surprising that abnormalities of these key mediators, molecules that are important enough to be conserved through evolution, may be involved in disease processes. What might not have been predicted was that removal of a single upregulated cytokine can make a clinical difference. This is best documented for anti-TNF (2) but is also true for blockade of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-1. In this review, we will summarize the current state of knowledge about cytokine expression and dysregulation in rheumatoid arthritis (RA) and other diseases and the role of TNF, the great majority of which is produced by macrophages. The knowledge gained has impacted our understanding of and therapy for other diseases also, and by focusing on cytokines, major rate-limiting steps, and hence therapeutic targets, there are opportunities for planning of therapy for many unmet needs.