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

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.

[1]  S. Maier,et al.  Prior Stressor Exposure Sensitizes LPS-Induced Cytokine Production , 2002, Brain, Behavior, and Immunity.

[2]  I. Hirsch,et al.  A Path Model of Chronic Stress, the Metabolic Syndrome, and Coronary Heart Disease , 2002, Psychosomatic medicine.

[3]  T. Patterson,et al.  Health Consequences of Alzheimer’s Caregiving Transitions: Effects of Placement and Bereavement , 2002, Psychosomatic medicine.

[4]  S. Maier,et al.  Prior stressor exposure primes the HPA axis , 2002, Psychoneuroendocrinology.

[5]  M. Irwin.  Psychoneuroimmunology of Depression: Clinical Implications , 2002, Brain, Behavior, and Immunity.

[6]  R. MacCallum,et al.  Long-term caregiving: what happens when it ends? , 2001, Journal of abnormal psychology.

[7]  J. Manson,et al.  C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. , 2001, JAMA.

[8]  Bonnie K. Lind,et al.  Involvement in caregiving and adjustment to death of a spouse: findings from the caregiver health effects study. , 2001, JAMA.

[9]  E. Bosmans,et al.  The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system. , 2001, Journal of affective disorders.

[10]  Qingbo Xu,et al.  Chronic Infections and the Risk of Carotid Atherosclerosis Prospective Results From a Large Population Study , 2001 .

[11]  L. Ferrucci,et al.  Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[12]  T. Harris,et al.  The Prognostic Value of Serum Albumin in Healthy Older Persons with Low and High Serum Interleukin‐6 (IL‐6) Levels , 2000, Journal of the American Geriatrics Society.

[13]  R. MacCallum,et al.  Chronic Stress Modulates the Immune Response to a Pneumococcal Pneumonia Vaccine , 2000, Psychosomatic medicine.

[14]  M Irwin,et al.  Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. , 2000, The Journal of clinical endocrinology and metabolism.

[15]  P. Ridker,et al.  Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. , 2000, Circulation.

[16]  R. Schulz,et al.  Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. , 1999, JAMA.

[17]  K. Buckwalter,et al.  Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[18]  D. Papanicolaou,et al.  Circadian interleukin-6 secretion and quantity and depth of sleep. , 1999, The Journal of clinical endocrinology and metabolism.

[19]  Luigi Ferrucci,et al.  Serum IL‐6 Level and the Development of Disability in Older Persons , 1999, Journal of the American Geriatrics Society.

[20]  H. Cohen,et al.  Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. , 1999, The American journal of medicine.

[21]  E. Bosmans,et al.  Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events , 1999, Biological Psychiatry.

[22]  T. Patterson,et al.  Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers. , 1999, Journal of psychosomatic research.

[23]  K. Vedhara,et al.  Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination , 1999, The Lancet.

[24]  H. Cohen,et al.  Association of Interleukin‐6 and Other Biologic Variables with Depression in Older People Living in the Community , 1999, Journal of the American Geriatrics Society.

[25]  R. Dantzer,et al.  Cytokines and depression: fortuitous or causative association? , 1999, Molecular Psychiatry.

[26]  E. Bosmans,et al.  The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. , 1998, Cytokine.

[27]  D. Papanicolaou,et al.  The Pathophysiologic Roles of Interleukin-6 in Human Disease , 1998, Annals of Internal Medicine.

[28]  E. Bosmans,et al.  Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. , 1997, Cytokine.

[29]  P. Deuster,et al.  Exercise and Circadian Rhythm-Induced Variations in Plasma Cortisol Differentially Regulate Interleukin-1β (IL-1β), IL-6, and Tumor Necrosis Factor-α (TNFα) Production in Humans: High Sensitivity of TNFα and Resistance of IL-6 , 1997 .

[30]  D. Papanicolaou,et al.  Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. , 1997, The Journal of clinical endocrinology and metabolism.

[31]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[32]  J. Sheridan,et al.  Chronic stress alters the immune response to influenza virus vaccine in older adults. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  W. Malarkey,et al.  Slowing of wound healing by psychological stress , 1995, The Lancet.

[34]  Cannon Jg.  Cytokines in Aging and Muscle Homeostasis , 1995 .

[35]  David R. Williams,et al.  Us socioeconomic and racial differences in health: patterns and explanations , 1995 .

[36]  M. C. Leske,et al.  Comparing self-reported and physician-reported medical history. , 1994, American journal of epidemiology.

[37]  B. Rabin,et al.  Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. , 1993, Endocrinology.

[38]  J. Mullan,et al.  The bereaved caregiver: a prospective study of changes in well-being. , 1992, The Gerontologist.

[39]  Anthony S. Bryk,et al.  Hierarchical Linear Models: Applications and Data Analysis Methods , 1992 .

[40]  S. Harlow,et al.  A longitudinal study of risk factors for depressive symptomatology in elderly widowed and married women. , 1991, American journal of epidemiology.

[41]  M. Gilewski,et al.  The effects of late-life spousal bereavement over a 30-month interval. , 1991, Psychology and aging.

[42]  O. J. Trask,et al.  Spousal caregivers of dementia victims: longitudinal changes in immunity and health. , 1991, Psychosomatic medicine.

[43]  R. Schulz,et al.  Psychiatric and physical morbidity effects of caregiving. , 1990, Journal of gerontology.

[44]  Stuart Oskamp,et al.  The social psychology of health , 1990 .

[45]  B. Lebowitz,et al.  Alzheimer's disease treatment and family stress : directions for research , 1990 .

[46]  F. Sundler,et al.  Effect of 20 weeks' ranitidine treatment on plasma gastrin levels and gastric enterochromaffin-like cell density in the rat. , 1990, Digestion.

[47]  T. Bush,et al.  Self-report and medical record report agreement of selected medical conditions in the elderly. , 1989, American journal of public health.

[48]  J. House,et al.  Social relationships and health. , 1988, Science.

[49]  J. Kiecolt-Glaser,et al.  Methodological issues in behavioral immunology research with humans , 1988, Brain, Behavior, and Immunity.

[50]  L. Solberg,et al.  Smoking patterns among social contacts of smokers, ex-smokers, and never smokers: the Doctors Helping Smokers Study. , 1987, Preventive medicine.

[51]  A. Beck,et al.  Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation , 1988 .

[52]  Letitia Anne Peplau,et al.  Loneliness: A Sourcebook of Current Theory, Research and Therapy. , 1984 .

[53]  G. Fillenbaum,et al.  The development, validity, and reliability of the OARS multidimensional functional assessment questionnaire. , 1981, Journal of gerontology.