Interleukin-6, C-Reactive Protein, and Tumor Necrosis Factor-Alpha as Predictors of Mortality in Frail, Community-Living Elderly Individuals

OBJECTIVES: To investigate whether interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) protein levels predict all-cause mortality in older persons living in the community. DESIGN: Prospective cohort study. SETTING: Data were from the Aging and Longevity Study in the Sirente Geographic Area, a prospective cohort study. PARTICIPANTS: Individuals aged 80 and older living in an Italian mountain community (N = 362). MEASUREMENTS: Participants were classified according to the median value of the three inflammation markers (IL-6, 2.08 pg/mL; TNF-alpha, 1.43 pg/mL; CRP, 3.08 mg/L). A composite summary score of inflammation was also created. The main outcome was risk of death after 4 years of follow-up. RESULTS: One hundred fifty deaths occurred during 4 years of follow-up. In the unadjusted model, high levels of each of the three markers were associated with greater mortality. After adjusting for potential confounders, high levels of IL-6 (hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.29-3.69) and CRP (HR = 2.58, 95% CI = 1.52-4.40) were associated with a significantly greater risk of death, whereas the association between TNF-alpha protein levels and mortality was no longer significant (HR = 1.26, 95% CI = 0.74-2.15). The composite summary score of inflammation was strongly associated with mortality, with the highest risk estimated for individuals with all three inflammatory markers above the median. CONCLUSION: Low levels of inflammatory markers are associated with better survival in older adults, independent of age and other clinical and functional variables. J Am Geriatr Soc 59: 1679-1685, 2011.