LOCUS-COERULEUS STIMULATION BY CORTICOTROPIN-RELEASING HORMONE SUPPRESSES IN-VITRO CELLULAR IMMUNE-RESPONSES

Previous studies have demonstrated that stressors alter cellular immun e system function, and increase the activity of locus coeruleus neuron s. Furthermore, stressors increase the release of corticotropin-releas ing hormone (CRH) and locus coeruleus neurons are activated by CRH. Th us, the present study examined whether activation of the locus coerule us by infusion of CRH modulates the function of blood and spleen lymph ocytes assessed in vitro. CRH (100 ng) was administered into the regio n of the locus coeruleus in awake rats 1 hr before spleen and peripher al blood lymphocytes were collected for culture with nonspecific mitog ens. Unilateral or bilateral microinfusion of CRH into the locus coeru leus produced a decrease in blood and spleen T-lymphocyte mitogenic re sponses to phytohemagglutinin, ConA, and an antibody to the T-lymphocy te antigen receptor. In contrast, infusion of saline into the locus co eruleus or CRH into the surrounding region of the dorsal pons did not alter spleen or blood lymphocyte responses. Plasma concentrations of a drenocorticotropic hormone, corticosterone, and IL-6 were increased by CRH infusion into the locus coeruleus. These results suggest that CRH -evoked activation of the locus coeruleus stimulates the hypophysial a drenal axis, possibly activates the sympathetic nervous system, and re sults in immunosuppression. Comparable changes in lymphocyte and hormo ne responses are produced by an aversive stimulus or a conditioned str essor, suggesting that activation of the locus coeruleus may be a comp onent of stressor-induced immune alterations.