Ventromedial hypothalamus suppresses splenic lymphocyte activity through sympathetic innervation

The ventromedial hypothalamic nucleus (VMH) has been proposed to be a locus intimately associated with sympathetic facilitation in peripheral tissues. To investigate a possible role of the VMH in controlling peripheral immune functions, we examined the effects of VMH stimulation on proliferative activity of lymphocytes isolated from the spleen in rats. Electrical stimulation of the VMH (2 s at every 30 s for 30 min) caused a remarkable decrease in the mitogenic response of splenic lymphocytes to Concanavalin A, whereas the stimulation of other hypothalamic regions such as the paraventricular nucleus did not show any significant effects. The suppressive effect of VMH stimulation was not influenced after adrenalectomy, suggesting a minor role of the adrenocortical system. In contrast, pretreatments with a ganglionic blocking agent (chlorisondamine) and a beta-adrenergic receptor antagonist (propranolol) completely reversed the suppressive effect. Surgical severing of the sympathetic nerves entering the spleen also reversed the effect of VMH stimulation. Together with the previous finding that VMH stimulation activates the splenic sympathetic nerves, it is concluded that the VMH suppresses the proliferative activity of splenic lymphocytes through the activation of sympathetic nerves via the beta-adrenergic pathway.