Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney

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.