Differential cellular immunolocalization of renal tumour necrosis factor-alpha production during ischaemia versus endotoxaemia.

Both renal ischaemia and endotoxaemia provoke renal dysfunction and cellular injury. Although the clinical manifestation of each insult is similar (global renal dysfunction), ischaemia and endotoxaemia induce different patterns of cellular injury. Tumour necrosis factor-alpha (TNF-alpha) has been implicated in both types of renal injury; however, it remains unknown whether differential cellular TNF-alpha expression accounts for these changes.

Early renal ischemia, with or without reperfusion, activates NFkappaB and increases TNF-alpha bioactivity in the kidney.

Purpose: Acute tubular necrosis (ATN) and the ensuing renal failure induced by ischemia and reperfusion injury (I/R) remain a major cause of morbidity and mortality among patients in the intensive care unit. Although it is well established that exogenous tumor necrosis factor-alpha (TNF) induces renal injury, it remains unknown whether ischemia and/or reperfusion activates the signaling mechanisms required for renal TNF production. We hypothesized that ischemia and/or reperfusion would activate the oxidant sensitive TNF transcription factor, nuclear factor kappa B (NFkappaB), and thereby lead to renal TNF production.

Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion.

The purpose of this study was to determine whether isolated renal ischemia and reperfusion (I/R) induces renal tumor necrosis factor (TNF) mRNA production, TNF protein expression, or TNF bioactivity and, if so, whether local/early TNF production acts as mediator of ischemia-induced, neutrophil-mediated renal injury. After rats were anesthetized, varying periods of renal ischemia, with or without reperfusion, were induced. Kidney mRNA content (RT-PCR), TNF protein expression (ELISA), TNF bioactivity (WEHI-164 cell clone cytotoxicity assay), and neutrophil infiltration [myeloperoxidase (MPO) assay] were determined.

Liposomal delivery of heat-shock protein 72 into the heart prevents endotoxin-induced myocardial contractile dysfunction.

Background: The purposes of this study were to (1) determine whether functional heat-shock protein 72 (HSP-72) may be delivered into the heart, (2) determine whether HSP-72 itself is protective against endotoxin (lipopolysaccharide [LPS]-induced cardiodepression, and (3) compare relative protection and time courses required for protection for thermally induced HSP-72 versus liposomally introduced HSP-72.

Methods: HSP-72 was introduced (liposomal HSP-72) or induced (heat shock, 42 degrees C x 15 minutes, 24 hours before) in rat heart before LPS administration (0.5 mg/kg intraperitoneal or ex vivo coronary infusion).

Role of TNF in mediating renal insufficiency following cardiac surgery: evidence of a postbypass cardiorenal syndrome.

Recent evidence has implicated proinflammatory mediators such as TNF-alpha in the pathophysiology of ischemia-reperfusion (I/R) injury. Clinically, serum levels of TNF-alpha are increased after myocardial infarction and after cardiopulmonary bypass. Both cardiopulmonary bypass and renal ischemia-reperfusion injury induce a cascade of events leading to cellular damage and organ dysfunction.