BACKGROUND: The serum concentration of interleukin 6 (IL‐6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age‐associated chronic diseases, which often cause disability, high circulating levels of IL‐6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL‐6 predict future disability in older persons who are not disabled. METHODS: Participants at the sixth annual follow‐up of the Iowa site of the Established Populations for Epidemiologic Studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living (ADL), and they were re‐interviewed 4 years later. Incident cases of mobility‐disability and of ADL‐disability were identified based on responses at the follow‐up interview. Measures of IL‐6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected randomly (46.9%) from those who continued to be non‐disabled. FINDINGS: Participants in the highest IL‐6 tertile were 1.76 (95% CI, 1.17‐2.64) times more likely to develop at least mobility‐disability and 1.62 (95% CI, 1.02‐2.60) times more likely to develop mobility plus ADL‐disability compared with to the lowest IL‐6 tertile. The strength of this association was almost unchanged after adjusting for multiple confounders. The increased risk of mobility‐disability over the full spectrum of IL‐6 concentration was nonlinear, with the risk rising rapidly beyond plasma levels of 2.5 pg/mL. INTERPRETATION: Higher circulating levels of IL‐6 predict disability onset in older persons. This may be attributable to a direct effect of IL‐6 on muscle atrophy and/or to the pathophysiologic role played by IL‐6 in specific diseases. J Am Geriatr Soc 47:639–646, 1999.

Serum IL‐6 Level and the Development of Disability in Older Persons