title: Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthritis.
abstract: Clinical intervention studies have clearly shown the benefit in suppressing tumor necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence, considerable interest has arisen in those pathways that in turn regulate TNF-alpha production, because they may offer further possible therapeutic targets. Several candidate pathways are currently being investigated. They include T cell/macrophage interactions mediated primarily through cell-cell membrane contact; novel cytokine activities; microbial-derived products, in particular bacterial deoxyribonucleic acid sequences; autoreactive T cells, and immunoglobulins. At the subcellular level, there is further interest in targeting signaling and mRNA processing and cytokine cleavage pathways required for optimal TNF-alpha production. The key recent observations in these areas, particularly in the extracellular compartment, are reviewed.
authors: Center for Rheumatic Diseases and Department of Immunology, University of Glasgow, Glasgow, UK.
authors: J Alastair
authors: JA
authors: Gracie
authors: Bernard P
authors: BP
authors: Leung
authors: Iain B
authors: IB
authors: McInnes
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D018407:Bacterial Physiological Phenomena; D002450:Cell Communication / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha