Sympathetic nervous responses during cytokine-induced fever in conscious rabbits

Sympathetic responses during fever induced by two representative endogenous pyrogens, interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha), and their effective inducer, lipopolysaccharide (LPS), were investigated in conscious rabbits. Rectal temperature, ear skin temperature as an index for the ear skin sympathetic nerve activity (ESNA), renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were recorded during fever induced by intravenous injection of these pyrogens. IL-1 beta (100 ng/kg) elicited a fever accompanied by a transient activation of ESNA and long-lasting increases in RSNA, MAP and HR. Subcutaneous indomethacin (20 mg/kg) significantly attenuated all the responses induced by IL-1 beta. TNF alpha (10 micrograms/kg) also elicited fever with increases in ESNA, RSNA and HR, while MAP was not affected. All the TNF-induced responses were totally blocked by indomethacin. LPS at two doses of 500 ng/kg and 1 microgram/kg elicited fever and increased ESNA, RSNA and HR. Only the larger dose induced hypotension. The present results show in conscious rabbits exposed to thermoneutral environment that these pyrogens activate sympathetic efferents in regionally differentiated time courses. The present results also suggest that arachidonate metabolites are involved not only in the thermoregulatory vasoconstrictor response in the ear and the body temperature increase but also in simultaneously evoked renal sympathetic and haemodynamic adjustments in fever.