Out of Balance: A New Look at Chronic Stress, Depression, and Immunity

Chronic stress is typically associated with suppression of the immune system, including impaired responses to infectious disease and delayed wound healing. Recent work suggests that stress and depression can enhance production of proinflammatory cytokines, substances that regulate the body’s immune response to infection and injury. We provide a broad framework relating stress and depression to a range of diseases whose onset and course may be influenced by proinflammatory cytokines, particularly the cytokine interleukin-6 (IL-6). IL-6 has been linked to a spectrum of chronic diseases associated with aging. Production of proinflammatory cytokines that influence these and other conditions can be directly stimulated by chronic stress and depression. We suggest that a key pathway through which chronic stress and depression influence health outcomes involves proinflammatory cytokines. We discuss the evidence for relationships between psychosocial factors and proinflammatory cytokines, and important health implications of these findings. KEYWORDS—chronic stress; depression; immunity; cytokines; inflammation A long-standing idea in the field of psychoneuroimmunology (the study of interactions between the nervous system and the immune system) is that chronic stress suppresses the immune system. A recent review of the past 30 years of research on stress and immunity concluded that ‘‘the most chronic stressors were associated with the most global immunosuppression’’ (Segerstrom & Miller, 2004, p. 618). Our own research has previously demonstrated that immune suppression related to chronic stress has clinical implications, including impaired immune responses to infectious disease and delayed wound healing. Currently, researchers are changing their thinking about the relations among chronic stress, depression, and immunity. Recent research suggests that chronic stress and depression may actually enhance certain immune responses. One immune response in question is inflammation, a broad term that refers to immune processes triggered by damage to cells and tissues. Such damage occurs in a variety of ways, including infection and injury. The immune system initiates inflammatory responses that are critical to resolving infections and repairing the damaged tissue. Focusing on the inflammation-enhancing role of chronic stress and depression marks an important shift in how researchers conceptualize the complex interactions between the brain, behavior, and the immune system. Rather than supporting the model in which chronic stress and depression results in global immune suppression, the evidence reviewed here suggests a more complex and clinically relevant model in which chronic stress and depression result more generally in immune dysregulation. The body normally orchestrates a balanced response when faced with immunological challenges, but in the new model, chronic stress and depression disrupt this balance, suppressing some immune responses and enhancing others. This can have significant costs to an individual’s physical health, including prolonged cell and tissue damage, increased vulnerability to acute and chronic diseases, and even premature aging. CYTOKINES AND IMMUNE REGULATION The key substances involved in regulating inflammatory responses to infection and injury are cytokines. Released by a variety of cells, cytokines are proteins that serve as intercellular C D I R 3 4 5 B Dispatch: 10.5.05 Journal: CDIR CE: Blackwell Journal Name Manuscript No. Author Received: No. of pages: 5 PE: Saravana/Mini Address correspondence to Janice K. Kiecolt-Glaser, Department of Psychiatry, Ohio State University College of Medicine, 1670 Upham Drive, Columbus, OH 43210-1228. CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE Volume 14—Number 2 111 Copyright r 2005 American Psychological Society (B W U S C D IR 3 45 .P D F 10 -M ay -0 5 18 :1 1 52 74 8 B yt es 5 P A G E S n op er at or = C . M in i)