Research reportBrain vasopressin is involved in stress-induced suppression of immune function in the rat
Introduction
Stress induces various changes in the neuroendocrine system, the autonomic nervous system, behavior, mood, and the immune system. Among these changes, brain corticotropin-releasing hormone (CRH) plays important roles to integrate changes in stress, such as stimulation of the pituitary–adrenal axis [32], suppression of the pituitary–gonadal axis [33], stimulation of epinephrine secretion from the adrenal medulla [6], inhibition of gastric acid secretion [39], stimulation of the transit time of the colon [44], suppression of feeding behavior 25, 35, and increasing of arousal [37]and offensive mood [42]. In addition, recent studies have revealed that both intracerebroventricular (i.c.v.) administration of CRH and stress inhibit immune function, such as splenic natural killer (NK) cytotoxicity, the proliferative response of T cell in peripheral blood to a mitogenic agent, and specific antibody production to a novel antigen, and that brain CRH is involved in the mechanism of inhibition of the immune function by stress in rats 20, 21, 22.
The release of both vasopressin (VP) and CRH increases in response to stress, and VP as well as CRH participate in the mechanism of stimulation of the pituitary–adrenal axis in stress [32]. Besides the action on the pituitary–adrenal axis, evidence has accumulated suggesting the roles of VP in a variety of central nervous system functions, such as learning, memory, and the regulation of body temperature and cardiovascular system [13]. Further, VP is found to mediate emotional stress-induced colonic motor alterations, suggesting the involvement of central nervous system VP in various stress responses [7]. Therefore, the present study was designed to clarify whether brain VP is also involved in the stress-induced suppression of immune function in the rat. To this end, the effects of intracerebroventricular (i.c.v.) administration of a VP V1 receptor antagonist on the electrical footshock-induced suppression of the splenic T cell proliferative response to concanavalin A (con A), a T cell mitogenic agent, and splenic NK cytotoxicity were tested. Furthermore, the effects of i.c.v. administration of VP on the proliferative response of splenic T cells to con A and on splenic NK activity were examined in rats.
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Animals
Male Wistar rats weighing 180–200 g, individually housed under conditions of controlled temperature and illumination (0800–2000 h) and allowed ad libitum access to food and water, were used in this study. The right lateral ventricle (rostral, 0.0 mm; lateral, 1.8 mm; ventral, 5.0 mm, relative to the bregma and the dural surface) of the animals was implanted with a polyethylene guide cannula (length, 7.5 mm; i.d., 0.58 mm; o.d., 0.96 mm; Natsume, Tokyo, Japan) under sodium pentobarbital
Effects of V1 receptor antagonist and CRH receptor antagonist on footshock-induced suppression of immune function
Intermittent electrical footshock for 60 min significantly suppressed the proliferative response of T cells to 0.625, 1.25 or 2.5 μg/ml con A, and the suppression of the proliferative response of T cells to 2.5 μg/ml con A was partially attenuated by the i.c.v. administration of 75 ng of the V1 receptor antagonist (Fig. 1), while the suppression of NK cytotoxicity by intermittent electrical footshock for 60 min was completely blocked by the V1 receptor antagonist at an effector/target cell
Discussion
The present study demonstrated that footshock stress induces suppression of the proliferative response of T cells to the mitogen con A and NK cytotoxocity, as reported previously by other research groups 20, 22, and that the inhibition of the T cell proliferative response is partially, and that of NK cytotoxicity is completely, blocked by i.c.v. administration of a V1 receptor antagonist. In addition, we found that i.c.v. administration of VP suppresses the proliferative response of T cells to
Acknowledgements
This study was supported in part by a grant from the Japan Private School Promotion Foundation and a grant for anorexia nervosa from the Japanese Ministry of Health and Welfare.
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