Behavioral and neural influences on cellular immune responses: effects of stress and interleukin-1

A series of experiments examined effects of stressful conditions on several cellular immune responses and attempted to elucidate the physiological mechanisms underlying these effects. Initial studies showed that stressful conditions can profoundly suppress immune responses of blood and splenic lymphocytes, including T-cell mitogenesis, natural killer cell activity, production of interleukin-2 (IL-2) and interferon and IL-2 receptor expression. Subsequent studies found that (1) multiple physiological pathways mediate stress-induced suppression of these responses; (2) stress-induced suppression of these responses is produced, at least in part, by a peptide with molecular weight greater than 10 kilodaltons, which stressed animals release into circulation; (3) whereas most stressful conditions suppress immune responses, stressful conditions of moderate intensity can enhance cellular immune responses; and (4) extremely small quantities of interleukin-1 (IL-1) acting in the brain (e.g., 3.1-12.4 X 10(-15) moles) bring about suppression of cellular immune responses very rapidly and for a prolonged period of time. The relationship between the newly-discovered immunosuppressive influence of IL-1 in the brain and immunosuppression produced by stressful conditions remains to be determined.