title: TNF-blocking therapies: an alternative mode of action?
abstract: Despite expanding use of drugs blocking tumour necrosis factor (TNF), their precise mechanisms of action remain unclear. Early assumptions that they act by direct neutralization of the toxic inflammatory effects of TNF might be too simplistic because they explain neither the range of effects observed nor the varying properties of different TNF-blocking agents. Recent studies have demonstrated a key role for mast cell-derived TNF in the increase in lymph node size and the organizational complexity that accompanies a developing immune response. Regulation of this phenomenon might comprise a novel mode of action for TNF-directed therapy: by preventing this lymph node hyperplasia, TNF blockade could modulate immune responses, ameliorating pathology in autoimmune diseases, such as rheumatoid arthritis.
authors.affiliation: Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, Scotland, UK. bsck1p@clinmed.gla.ac.uk
authors.forename: Brian S W
authors.initials: BS
authors.lastname: Choo-Kang
authors.forename: Sharon
authors.initials: S
authors.lastname: Hutchison
authors.forename: Mohammad B
authors.initials: MB
authors.lastname: Nickdel
authors.forename: Robert V
authors.initials: RV
authors.lastname: Bundick
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leishman
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008407:Mast Cells; D018448:Models, Immunological; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha