Acute Renal Failure in Endotoxemia Is Caused by TNF Acting Directly on TNF Receptor-1 in Kidney

Abstract

Bacterial endotoxin (LPS) is responsible for much of the widespread inflammatory response seen in sepsis, a condition often accompanied by acute renal failure (ARF). In this work we report that mice deficient in TNFR1 (TNFR1^−/−) were resistant to LPS-induced renal failure. Compared with TNFR1^+/+ controls, TNFR1^−/− mice had less apoptosis in renal cells and fewer neutrophils infiltrating the kidney following LPS administration, supporting these as mediators of ARF. TNFR1^+/+ kidneys transplanted into TNFR1^−/− mice sustained severe ARF after LPS injection, which was not the case with TNFR1^−/− kidneys transplanted into TNFR1^+/+ mice. Therefore, TNF is a key mediator of LPS-induced ARF, acting through its receptor TNFR1 in the kidney.