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.