Proinflammatory Cytokine Tumor Necrosis Factor-Alpha

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 7 No. 4 • September 2004

Proinflammatory Cytokine Tumor Necrosis Factor-Alpha Increases with Hostility and Aggression

Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory cytokine that has been implicated in the pathogenesis of cardiovascular disease.1 TNF-alpha is released at all stages of inflammation associated with atherogenesis, promoting the expression of adhesion molecules on endothelial cells that contribute to cells such as macrophages accumulating at the site of atherogenic lesions, and it also triggers the release of the pro-inflammatory cytokine IL-6, which has been reported to be associated with the risk of future heart attacks in healthy men.2 TNF-alpha also increases the concentrations of C-reactive protein, another inflammatory risk factor for cardiovascular disease.1

The authors1 report that increased TNF-alpha has also been linked to depression. The study examined 62 healthy, nonsmoking men aged 18–45 years. They were assessed for aggression, hostility, and anger, using the 29-item Buss and Perry aggression questionnaire (BPAQ), which is said to be widely used. The subjects also had blood samples evaluated for TNF-alpha expression. Results showed that higher total scores on the BPAQ were significantly associated with greater LPS-stimulated TNF-alpha expression (LPS is lipopolysaccharide, a bacterial cell-membrane component). Higher scores on the BPAQ were associated with higher TNF-alpha levels.

Hence, men who exhibited higher levels of hostility and aggression, as measured by the test, had higher levels of TNF-alpha expression in response to LPS. The authors note that the triad of aggression, hostility, and anger is inversely associated with serotonergic activity and that serotonin inhibits monocyte-associated TNF-alpha production induced by exposure to LPS. This suggests that supplementation with tryptophan or 5-hydroxytryptophan may reduce aggression, hostility, and anger and the increased TNF-alpha response to LPS. In severe cases, however, fluoxetine, the most selective SSRI, may be helpful.

Moderate alcohol consumption may also help.3 A paper reports that moderate alcohol consumption (2 alcoholic drinks a day) in 8 healthy men resulted in 39% reduction (gin) or 96% reduction (red wine) in monocyte adhesion after TNF-alpha stimulation of endothelial cells.

  1. Suarez et al. The relation of aggression, hostility, and anger to lipopolysaccharide-stimulated tumor necrosis factor (TNF)-alpha by blood monocytes from normal men. Brain, Behavior, Immunity 16:675-84 (2002).
  2. Ridker et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767-72 (2000).
  3. Badia et al. Decreased tumor necrosis factor-induced adhesion of human monocytes to endothelial cells after moderate alcohol consumption. Am J Clin Nutr 80:225-30 (2004).

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