The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk

• Published in: Journal of lipid research Vol. 48; no. 4; pp. 751 - 762
• Main Authors: Popa, Calin, Netea, Mihai G., van Riel, Piet L.C.M., van der Meer, Jos W.M., Stalenhoef, Anton F.H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2007; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: anti-tumor necrosis factor; Cardiovascular Diseases - etiology; Chronic Disease; Humans; Inflammation - etiology; insulin resistance; Lipid Metabolism; lipids; Risk; Tumor Necrosis Factor-alpha - physiology; tumor necrosis factor-α; anti-tumor necrosis factor; lipids; insulin resistance; tumor necrosis factor-α
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.R600021-JLR200

The recent insight that inflammation contributes to the development of atherosclerosis and type 2 diabetes mellitus constitutes a major breakthrough in understanding the mechanisms underlying these conditions. In addition, it opens the way for new therapeutic approaches that might eventually decrease the prevalence of these public health problems. Tumor necrosis factor-α (TNF-α) has been shown to play a key role in these processes and thus might be a potential therapeutic target. Increased concentrations of TNF-α are found in acute and chronic inflammatory conditions (e.g., trauma, sepsis, infection, rheumatoid arthritis), in which a shift toward a proatherogenic lipid profile and impaired glucose tolerance occurs. Although therapeutic blockade of TNF-α worsens the prognosis in patients with abscesses and granulomatous infections, this strategy is highly beneficial in the case of chronic inflammatory conditions, including rheumatoid arthritis. Current investigations assessing the impact of anti-TNF agents on intermediary metabolism suggest that TNF-α blockade may improve insulin resistance and lipid profiles in patients with chronic inflammatory diseases.