Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

Elevated levels of tumor necrosis factor alpha and mortality in centenarians in The American Journal of Medicine, Helle Bruunsgaard, MD, PhDemail, Karen Andersen-Ranberg, MD, PhD, Jacob v.B Hjelmborg, MS, PhD, Bente Klarlund Pedersen, DMSc, Bernard Jeune, MD
Received: October 30, 2002; Accepted: April 29, 2003

Abstract"

Background
Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) a initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-a was also a prognostic marker for all-cause mortality in these persons.

Methods
We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-a, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during the subsequent 5 years.

Results
Only 9 subjects were alive after 5 years. Elevated levels of TNF-a were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C-reactive protein were not associated with mortality when levels of TNF-a were included in the analysis. Dementia and cardiovascular diseases represented the major causes of comorbid conditions at baseline. TNF-a was still associated with mortality in multivariate models that included these parameters as confounders.

Conclusion
TNF-a was an independent prognostic marker for mortality in persons aged 100 years, suggesting that it has specific biological effects and is a marker of frailty in the very elderly.

Article at:
http://www.amjmed.com/article/S0002-9343(03)00329-2/abstract