Immune response of stressed rats treated with drugs affecting serotoninergic and adrenergic transmission.

Stressful conditions interfere with immune response. One of the principal mechanisms is activation of hypothalamo-pituitary-suprarenal axis by central serotoninergic and adrenergic pathways. Alternative mechanisms bypassing the axis also take part in stress-induced immunomodulation. Immunosuppression caused by repeated restraints or over-crowding was usually accompanied by increased metabolism of serotonin in the brain (as indicated by increased level of its metabolite, 5-HIAA) and by increased levels of corticosterone in plasma. Changes in lymphatic tissues of stressed animals that result in suppression of immune response apparently "outlive" fluctuating changes in neurotransmitter and corticosterone levels. Drugs that alter serotoninergic or adrenergic transmission interfere with immunosuppressive effect of stress either synergistically (augmenting suppression) or antagonistically (preventing it). Since immunocompetent cells possess serotoninergic and adrenergic receptors, such drugs may exert their effect either via central neuroendocrine mechanisms, or by direct effects on immunocompetent cells.

Immunological and neuroendocrine responses of rats to prolonged or repeated stress.

Stress by overcrowding lasting 2 weeks or more depressed the Arthus reaction in rats, and repeated immobilization for 4 days depressed the plaque-forming cell (PFC) response in Jerne's assay. The concentrations of neurotransmitters in the brain showed 2 peaks during the overcrowding: at the beginning of the stress (day 2) there was a sharp rise of 5-hydroxy-indoleacetic acid (5-HIAA), a metabolite of serotonin, and in the second week (day 10) there was another rise of 5-HIAA, together with serotonin and noradrenaline. Plasma corticosterone showed an initial drop, followed by increase that also culminated on day 10 of the stress, indicating adaptation. Other stressful procedures (daily immobilizations, repeated injections of picrotoxin) alos changed the levels of neurotransmitter substances and glucocorticoid hormones. A conspicuous feature noted in all models was coincidence of increased 5-HIAA (indicating increased metabolism of serotonin) with either increase of fall of the corticosterone level in plasma. This seems to be related to the state of immunosuppression. Studies on the effects of stress on immunity in parallel with neuroendocrine responses, may give insight into possible neuroendocrine control of immune phenomena.