Stress-induced alterations of immunity in hypophysectomized rats.

Abstract

Stress-induced suppression of mitogeninduced lymphocyte proliferation was demonstrated in hypophysectomized rats. Stress effects on the numbers of peripheral blood lymphocytes and lymphocyte subsets and on splenic natural killer cell activity require the presence of pituitary. A pituitary-dependent restraining influence on stress-induced alteration of immunity is described. These results indicate that stress-induced modulation ofimmunity is complex and includes a range of enhancing and inhibitory mechanisms.A wide range of stressors alter immunity in animals and humans. The specific mechanisms that mediate these stress effects have not been fully elucidated. The endocrine system is highly responsive to stress and neuroendocrine activity and, through the hypothalamic-pituitary axis, may be involved in stress-induced alterations of the immune system. The secretion of corticosteroids has long been considered the mechanism of stress-induced modulation of immunity. We have shown stress-induced suppression of lymphocyte proliferation in adrenalectomized rats, indicating that corticosteroid-independent mechanisms participate in stress-related modulation of immunity (1). Because a variety of other hormones under pituitary control have been associated with immunoregulatory processes (2), we investigated the role of the pituitary in mediating stress-induced alterations of immunity, examining the effects of a stressor on immune function in hypophysectomized rats. MATERIALS AND METHODSA total of 96 Sprague-Dawley male rats (Zivic-Miller, Pittsburgh) and a "3 x 2" experimental design (16 rats per group) were used. The three groups consisted of nonoperated, sham-hypophysectomized, and hypophysectomized rats. The two treatments, home cage controls and stressed animals, were similar to those used in our previous studies (1, 3) with the level of shock 0.6 mA for the first 6 hr, 1.2 mA for the second 6 hr, and 1.8 mA for the final 6 hr. In our previous studies, we used the Wistar-Furth strain of rat and a stress schedule that had been shown to elicit a classic stress response (1, 3). In the present study, we used the SpragueDawley strain of rat, since this animal is hardier and thereby better suited for experiments requiring hypophysectomy. In a series of preliminary studies, we titrated the intensity of the electric shock to the minimum level that would allow the differentiation between home cage and stressed animals in terms of the phytohemagglutinin (PHA) response.Hypophysectomy and sham hypophysectomy were performed by standard techniques (Zivic-Miller) Two to 3 weeks were allowed for recovery from operative procedures. All animals were given free access to food, tap water, and a saline solution, and were maintained in a quiet room with the temperature carefully regulated at 70'F (21.10C). All experiments were conducted at the same time of day.After the shock period, the rats were removed from the apparatus or home cages, anesthetized with ether, and exsanguinated by heart puncture within 3 min using preservative-free...

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