Role for TNF in atherosclerosis? Lessons  from autoimmune disease.
Inflammatory pathways have been implicated in the initiation and progression of cardiovascular diseases. Accelerated atherosclerosis has been described in patients with chronic inflammatory diseases, particularly rheumatoid arthritis, disproportionate to individuals' detectable traditional vascular risk factors. This finding suggests that other pathways associated with inflammation might account for increased vascular risk in such diseases. Highly specific biologic agents can precisely block the activity of cytokines generated during inflammatory cascades; the effects of these inflammatory moieties on vascular physiology and overall risk of cardiovascular events has been directly evaluated. This review summarizes key epidemiologic, physiologic and model data, which together suggest that tumor necrosis factor, a pivotal cytokine in the inflammatory cascade, is directly involved in vascular pathophysiology and that its inhibition might confer an overall advantage to the recipient. Moreover, such data obtained in chronic inflammatory diseases likely have relevance to primary atherosclerosis.
Center for Rheumatic Diseases, Glasgow, Royal Infirmary, Glasgow, UK.
Gayle E
GE
McKellar
David W
DW
McCarey
Naveed
N
Sattar
Iain B
IB
McInnes
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001158:Arteries / Q000276:immunology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002908:Chronic Disease; D004548:Elasticity; D004730:Endothelium, Vascular / Q000276:immunology / Q000503:physiopathology; D006333:Heart Failure / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000276:immunology; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha