Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy

Section: Discussionmentioning

confidence: 89%

Netrin-1 regulates colon-kidney cross talk through suppression of IL-6 function in a mouse model of DSS-colitis

Ranganathan

Jayakumar

Manicassamy

et al. 2013

“…Renal ischemia provokes a systemic inflammatory response, and among the recognized and prominent cytokines so produced is IL-6. Such a systemic response is implicated in the adverse distant effects of renal ischemia such as lung injury (23). Clinical observations in acutely ill patients demonstrate that plasma IL-6 levels predict ventilator dependency, severity of acute kidney injury, and mortality that occur in this patient population (6,29,44).…”

Section: Discussionmentioning

confidence: 99%

Genetic deficiency of Smad3 protects against murine ischemic acute kidney injury

Nath

Croatt

Warner

et al. 2011

TGF-β1 contributes to chronic kidney disease, at least in part, via Smad3. TGF-β1 is induced in the kidney following acute ischemia, and there is increasing evidence that TGF-β1 may protect against acute kidney injury. As there is a paucity of information regarding the functional significance of Smad3 in acute kidney injury, the present study explored this issue in a murine model of ischemic acute kidney injury in Smad3+/+ and Smad3−/− mice. We demonstrate that, at 24 h after ischemia, Smad3 is significantly induced in Smad3+/+ mice, whereas Smad3−/− mice fail to express this protein in the kidney in either the sham or postischemic groups. Compared with Smad3+/+ mice, and 24 h following ischemia, Smad3−/− mice exhibited greater preservation of renal function as measured by blood urea nitrogen (BUN) and serum creatinine; less histological injury assessed by both semiquantitative and qualitative analyses; markedly suppressed renal expression of IL-6 and endothelin-1 mRNA (but comparable expression of MCP-1, TNF-α, and heme oxygenase-1 mRNA); and no increase in plasma IL-6 levels, the latter increasing approximately sixfold in postischemic Smad3+/+ mice. We conclude that genetic deficiency of Smad3 confers structural and functional protection against acute ischemic injury to the kidney. We speculate that these effects may be mediated through suppression of IL-6 production. Finally, we suggest that upregulation of Smad3 after an ischemic insult may contribute to the increased risk for chronic kidney disease that occurs after acute renal ischemia.

“…In the lungs, animal models of bilateral nephrectomy show increased TNF-␣ and IL-6, which lead to uncontrolled systemic inflammation, neutrophil infiltration, and impaired vascular permeability resulting in pulmonary edema (27). Renal ischemia reperfusion in rats leads to increased TNF-␣, IL-1, and intercellular adhesion molecule-1 mRNA and myeloperoxidase activity in the heart, resulting in left ventricular dysfunction at 48 h after reperfusion (25).…”

Section: Discussionmentioning

confidence: 99%

Cytokine elevation and transaminitis after laparoscopic donor nephrectomy

Yap

Park

Egan

et al. 2012

Yap S, Park SW, Egan B, Lee HT. Cytokine elevation and transaminitis after laparoscopic donor nephrectomy. Am J Physiol Renal Physiol 302: F1104 -F1111, 2012. First published January 18, 2012 doi:10.1152/ajprenal.00543.2011.-Acute kidney injury frequently occurs in the critically ill and often progresses into multiorgan dysfunction syndrome, resulting in high mortality. We previously showed that nephrectomized mice had increased interleukin (IL)-6 and tumor necrosis factor (TNF)-␣ that directly contributed to systemic inflammation and hepatic injury. In this study, we examined whether patients undergoing laparoscopic donor nephrectomy have increased postoperative cytokine levels with injury to the liver and whether the remaining kidney sustains injury. Serial serum and urine samples were collected from 32 patients undergoing laparoscopic donor nephrectomy and 17 patients undergoing nonrenal laparoscopic surgery. Serum IL-6, IL-18, TNF-␣ and monocyte chemotactic protein-1 (MCP-1) (markers of systemic inflammation) and urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), MCP-1, and IL-18 (markers of acute kidney injury) were quantified by enzyme-linked immunosorbent assay. We also analyzed serum creatinine, aspartate transaminase (AST), and alanine transaminase to assess liver injury. Patients who underwent donor nephrectomy not only demonstrated increased serum creatinine but also had significant increases in serum IL-6, MCP-1, and AST. Serum TNF-␣ also trended upward in donor nephrectomy patients. Finally, the donor nephrectomy group showed increased urinary NGAL but not KIM-1 at 24 h. Taken together, our findings of increased serum IL-6, MCP-1, and AST after donor nephrectomy suggest that an acute reduction of kidney function induces systemic inflammation and may have distant effects on the liver. Further studies are needed to correlate increased urinary NGAL after donor nephrectomy both as a potential marker for renal tubular stress and/or hypertrophy in the contralateral kidney.acute kidney injury; interleukin-6; neutrophil gelatinase-associated lipocalin; tumor necrosis factor-␣ ACUTE KIDNEY INJURY (AKI) is a frequent occurrence in the critically ill with 5% to 20% of patients experiencing an episode of AKI during their intensive care unit stay (46). Mortality in critically ill patients with AKI remains high and is estimated to be Ͼ50% (54). Even when controlled for the severity of illness, AKI confers an independent risk for mortality regardless of whether AKI is mild or treated with renal replacement therapy (30). Hence, understanding the specific extrarenal effects of AKI in propagating or exacerbating multiorgan dysfunction is essential, since it may lead to new therapies in decreasing mortality after AKI.In animal models, it is increasingly clear that AKI is not an isolated event and induces distant organ dysfunction to the lungs, heart, liver, and brain through a mechanism that involves neutrophil migration and elevated cytokine levels (14).In particular, hepat...