Actions of interferonα and interleukin-1β on the glucose-responsive neurons in the ventromedial hypothalamus

Abstract

Effects of recombinant interferonα (rhIFNα) and interleukin-1β (rhIL-1β) on the activity of glucose-responsive and glucose-unresponsive neurons in the ventromedial hypothalamus (VMH) were investigated with rat tissue slice preparations. While the majority of neurons which increased the activity in response to a rise in glucose concentration were excited by perfusion of rhIFNα (100–5000 U/ml) and rhIL-1β (40–160 ng/ml), most of the neurons which increased their activity to a fall in glucose concentration were inhibited by rhIFNα and rhIL-1β. The majority of glucose-unresponsive neurons were not affected by the cytokines. These neuronal responses are appropriate in explaining the anorexia induced by IFNα and IL-1. Concurrent application of sodium salicylate, an inhibitor of prostaglandin synthesis, blocked both the increase and decrease in activities of VMH neurons by rhIL-1β, but not those by rhIFNα. Alpha-melanocyte stimulating hormone (α-MSH) (8 × 10 −9−6.4 × 10 −7 M), an endogenous antipyretics and a possible antagonist of IL-1 at lymphocytes, specifically depressed the responses to rhIL-1β, but not those to rhIFNα. As has been previously shown in preoptic and anterior hypothalamic neurons, naloxone could block the responses of VMH neurons to rhIFNα, suggesting the opioid receptor mediation of IFNα's actions on the VMH neurons.