α-Melanocyte–stimulating Hormone Inhibits Lung Injury after Renal Ischemia/Reperfusion

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Abstract
Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock or visceral or renal ischemia. α-Melanocyte–stimulating hormone (α-MSH) is an antiinflammatory cytokine, which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if α-MSH inhibits acute lung injury after renal ischemia and to determine the early mechanisms of α-MSH action. Mice were subjected to renal ischemia treated with vehicle or α-MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of nuclear factor-κB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for intracellular adhesion molecule-1 and tumor necrosis factor-α. Renal ischemia rapidly activated kidney and lung nuclear factor-κB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury. α-MSH administration immediately before reperfusion significantly decreased kidney and lung injury and prevented activation of kidney and lung transcription factors and stress response genes, and lung intracellular adhesion molecule-1 and tumor necrosis factor-α at early time points after renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after renal ischemia. α-MSH protects against both kidney and lung damage after renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury.

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