This article presents a meta-analysis of the literature on stress and immunity in humans. The primary analyses include all relevant studies irrespective of the measure or manipulation of stress. The results of these analyses show substantial evidence for a relation between stress and decreases in functional immune measures (proliferative response to mitogens and natural killer cell activity). Stress is also related to numbers and percent of circulating white blood cells, immunoglobulin levels, and antibody titers to herpesviruses. Subsequent analyses suggest that objective stressful events are related to larger immune changes than subjective self-reports of stress, that immune response varies with stressor duration, and that interpersonal events are related to different immune outcomes than nonsocial events. We discuss the way neuroendocrine mechanisms and health practices might explain immune alteration following stress, and outline issues that need to be investigated in this area.

A meta-analysis indicated that clinical depression was associated with several large alterations in cellular immunity. Analyzing only methodologically sound studies, reliable immune alterations included lowered proliferative response of lymphocytes to mitogens (effect size rs = .24-.45), lowered natural killer cell activity (r = .28), and alterations in numbers of several white blood cell populations (rs = .11-.77). Immune alterations were greater in both older and hospitalized samples. There was also evidence of a linear relation between intensity of depressive affect and indicators of cellular immunity. Estimates of sample sizes needed to detect reliable effects for each immune outcome are provided. How neuroendocrine mechanisms or health practices might link depression to immunity is discussed, and design features needed to better understand these pathways are specified.

This review addresses the importance of studies of human psychoneuroimmunology in understanding the role of psychological factors in physical illness. First, it provides psychologically and biologically plausible explanations for how psychological factors might influence immunity and immune system-mediated disease. Second, it covers substantial evidence that factors such as stress, negative affect, clinical depression, social support, and repression/denial can influence both cellular and humoral indicators of immune status and function. Third, at least in the case of the less serious infectious diseases (colds, influenza, herpes), it considers consistent and convincing evidence of links between stress and negative affect and disease onset and progression. Although still early in its development, research also suggests a role of psychological factors in autoimmune diseases. Evidence for effects of stress, depression, and repression/denial on onset and progression of AIDs and cancer is less consistent and inconclusive, possibly owing to methodological limitations inherent in studying these complex illnesses, or because psychological influences on immunity are not of the magnitude or type necessary to alter the body's response in these cases. What is missing in this literature, however, is strong evidence that the associations between psychological factors and disease that do exist are attributable to immune changes.

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Objectives: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship. Methods: We studied 32 women who met Diagnostic and Statistical Manual of Mental Disorder, fourth edition, criteria for major depressive disorder and 32 healthy female control subjects. The groups were matched for age and ethnicity. None were taking medication, and all were free of disease involving the immune system. Results: Depressed subjects had reduced proliferative responses to the mitogens concanavalin A and phytohemagglutinin compared with control subjects. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation. Conclusions: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.