THE INFLUENCE OF INTERLEUKIN-2 ON THE RELEASE OF SOMATOSTATIN AND GROWTH HORMONE-RELEASING HORMONE BY MEDIOBASAL HYPOTHALAMUS

Interleukin-2 (IL-2), which plays a major role in the bidirectional intercellular communication between the neuroendocrine and immune systems, suppressed the release of GH from anterior pituitary halves at femtomolar concentrations. It is well established that the release of GH from the anterior pituitary is regulated by growth hormone releasing hormone (GRH) and growth hormone release-inhibiting hormone (somatostatin). Consequently, we studied the possible effect of Il-2 on the release of somatostatin and GRH from the mediobasal hypothalamus (MBH) in vitro. Single MBHs were incubated with fresh Krebs-Ringer bicarbonate (KRB) buffer alone or KRB containing different concentrations of IL-2 (10(-15)-10(-10) M) for 30 min. After collection of the media, the MBHs were incubated with KRB containing high potassium (high K+ = 56 mM) without IL-2 for a period of 30 min to study the effect of pretreatment with IL-2 on depolarization-induced somatostatin and GRH release. Experiments were also undertaken to study the effect of IL-2 in the presence of high K+ or IL-2 in the presence of DA (60 mum), a potent stimulator of somatostatin and GRH release. The minimal effective dose of IL-2 which significantly stimulated the release of somatostatin was 10(-14) M. Depolarization-induced release of somatostatin was reduced significantly by prior treatment with all the concentrations of IL-2 tested (10(-13)-10(-10) M). Basal release of GRH was unaltered by the different concentrations of IL-2 but the depolarization-induced release of GRH was significantly lowered by IL-2 (10(-13)-10(-10) M). Simultaneous incubation with IL-2 plus high K+ resulted in a significant decrease in GRH release without modifying the release of somatostatin. DA stimulated the release of both somatostatin and GRH; however, when IL-2 was added to DA, it significantly attenuated both DA-induced somatostatin and GRH release. The results demonstrate the ability of IL-2 to (1) stimulate somatostatin release without affecting GRH release; (2) suppress depolarization induced somatostatin release; (3) suppress depolarization-induced GRH release; and (4) block DA-induced stimulation of both somatostatin and GRH release, which suggests the possible involvement of a dopaminergic pathway in the mechanism of action of IL-2.