The onset of infection is associated with increases in renal blood flow and sodium excretion. Our studies provide evidence that the natriuresis is mediated by stimulation of renal prostaglandin production by the cytokine, interleukin-1. A dose-dependent natriuresis and diuresis was elicited in conscious rats with bolus intravenous injections of human recombinant interleukin-1-β (hrIL-1). Injection of 1.5, 3 and 24 μg hrIL-1 increased sodium excretion by 2.4 ± 0.9 μEq/min, 4.0 ± 0.8 μEq/min and 5.4 ± 0.3 μEq/min, respectively. The natriuresis was preceded by a corresponding increase in urinary PGE excretion (80%, 110% and 296%, respectively). The natriuresis elicited by 3 μg hrIL-1 was independent of changes in glomerular filtration rate or effective renal plasma flow. IL-1 induced an increase in rectal temperature, (0.6 ± 0.2°C) and a modest increase in mean arterial pressure (12 ± 3 mm Hg) within 10 minutes of injection. However, during the period of maximal natriuresis (40 to 100 min), blood pressure and rectal temperature were not signifantly different from control. Pretreatment with the cyclooxygenease inhibitor, ibuprofen, signficantly attenuated the natriuretic response and indomethacin completely abolished the natriuresis. These results identify IL-1 as a factor which stimulates renal PGE synthesis, and increases sodium excretion, independent of changes in glomerular filtration rate. We propose that IL-1-induced natriuresis may be a component of the overall acute phase response which is actively mounted by the host during infection.
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