Neuroendocrine mechanism of stress-induced immunosuppression and roles of cytokines.

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Various types of stressor suppress immune activities. Previously, we have confirmed a significant role of the sympathetic nervous system (SNS) in the stress-induced immunosuppression. In this study, we examined the effects of brain stimulation on the sympathetically mediated immunosuppression in rats. When the ventromedial hypothalamus (VMH), a putative hypothlamic center linked to the SNS,was stimulated electrically, the proliferative activity of splenic lymphocytes was reduced. The suppressive effect of VMH was not affected by adrenalectomy, but abolished by ganglionic blockade and surgical sympathetic denervation. These results suggest a critical role of the VMH in the stress-induced immunosuppression. Similar suppressive effects were also observed when interleukin-1 (IL-1), a representative cytokine produced in immune cells and brain cells, was given intracerebroventricularly. Brain IL-1 was also found to accelerate noradrenaline turnover in various peripheral organs, implying increased activity of the SNS.There are reports that the stress-induced immunosuppression was attenuated by intracranial injection of anti-IL-1 antibody. Collectively, it was concluded that brain IL-1 and the VMH play important roles in the stress-induced immunosuppression.