Chronic stress and age-related increases in the proinflammatory cytokine IL-6

Abstract

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Fig. 1.

Modeled change in IL-6 in caregivers vs. noncaregivers. The slope for caregivers, mean = 0.017(0.004), P < 0.001, was significant, whereas that for controls, mean = 0.004(0.003), P = 0.212, was not. Ninety-five percent confidence intervals for slopes were {0.009, 0.025} for caregivers and {-0.002, 0.010} for controls. The two slopes were significantly different from one another, χ²(1) = 6.66, P = 0.01, and caregivers' average rate of increase was about four times greater than that of noncaregivers.

Fig. 2.

Group differences in perceived stress scores (Upper) and loneliness [New York University Loneliness Scale (NYUL); Lower] by year. Caregivers consistently reported more stress, with group differences that were P = 0.05 or larger for all but year 6, with 1–6, respectively: t(157) = 4.70, P < 0.001; t(178) = 3.69, P < 0.001; t(165) = 1.98, P = 0.05; t(169) = 2.56, P = 0.01; t(168) = 2.01, P = 0.046; and t(143) = 0.97, P = 0.33. Similarly, caregivers consistently reported higher loneliness, with significant differences across all 6 years of the study, with 1–6 respectively: t(137) = 5.50, P < 0.001; t(167) = 4.84, P < 0.001; t(153) = 4.58, P < 0.001; t(169) = 3.02, P = 0.003; t(161) = 4.04, P < 0.001; and t(135) = 4.34, P < 0.001.