ANTIPYRESIS CAUSED BY STIMULATION OF VASOPRESSINERGIC NEURONS AND INTRASEPTAL OR SYSTEMIC INFUSIONS OF GAMMA-MSH

Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the site where its antipyretic effects are mediated in the brain was identified as the ventrolateral septum of the Limbic system. In guinea pigs, the majority of AVP projections to the septum originate from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8 V, current 0.205 a 0.017 mA) reduced the febrile response to an intramuscular injection of 20 mu g/kg lipopolysaccharide (LPS from Escherichia coli, 0111: B4) by 54% compared with unstimulated animals. This reduction in fever by electrical PVN stimulation was partly reversed by a simultaneous intraseptal microinfusion of the vasopressinergic V-1-receptor antagonist d(CH2)(5)[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion speed of 0.1 mu l/min. We further investigated the effects of intraseptal microinfusions or systemic infusions of the gamma-melanocyte stimulating hormone (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever. Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6 h with an infusion speed of 0.1 mu l/min caused a 38% reduction in fever. A significantly greater 57% reduction in fever was observed when the intraseptal microinfusion of gamma-MSH was combined with electrical stimulation of the PVN (for parameters see above). A systemic infusion of 0.261 mu mol gamma-MSH for 6 h reduced LPS fever to similar to 50% compared with animals infused with vehicle (0.9% saline). This antipyretic effect of peripherally administered gamma-MSH was not accompanied by a reduction of circulating levels of interleukin-6 and tumor necrosis factor. We conclude that in the complex process of endogenous antipyresis a number of bioactive peptides including AVP and gamma-MSH may be involved depending on the physiological situation.