Splenectomy attenuates the inappropriate diuresis associated with tumor necrosis factor administration

Tumor necrosis factor (TNF) is an important mediator of the systemic response to gram-negative sepsis and endotoxemia. We studied the renal effects of a sublethal TNF infusion in dogs (0.54=10⁵ international units per kilogram of body weight during a six hour period). The TNF-infused dogs (n=4) had marked polyuria and natriuresis in comparison with those in the control group (n=12) (urine output, 35.3±4.1 versus 3.7±0.5 millimeters per kilogram per six hours p<0.01; sodium excretion, 2.82±0.27 versus 0.75±0.19, p<0.01). To evaluate the role of the spleen in this response, seven dogs that had splenectomy were infused with TNF. Splenectomy abolished both the polyuria and the natriuresis; this could not be explained by the differences in fluid balance or in hemodynamic or metabolic alterations. Treatment with ibuprofen given intravenously (12.5 milligrams per kilogram 40 minutes before and three hours after the beginning of TNF infusion) in eight dogs that did not undergo splenectomy also abolished these renal effects. Prostaglandin 2 (PGE₂) concentrations in selected blood samples from the splenic vein did not increase with TNF infusion, excluding circulating PGE₂ as a possible mediator of the renal effects. The results of these studies indicate that, during septic challenge or severe inflammation, the spleen participates in signaling the kidney to increase water and sodium excretion. These renal events are mediated through the cyclo-oxygenase pathway.