-Melanocyte stimulating hormone inhibits lung injury after renal ischemia- reperfusion

Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock, or visceral or renal ischemia. -Melanocyte stimulating hormone ( MSH) is an anti-inflammatory cytokine which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if -MSH inhibits acute lung injury following renal ischemia, and to determine the early mechanisms of -MSH action. Mice were subjected to renal ischemia treated with vehicle or -MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of NFB, p38 MAPK, c-Jun, and AP-1 pathways, in addition to mRNA for ICAM-1 and TNF . Renal ischemia rapidly activated kidney and lung NFB, p38 MAPK, c-Jun, and AP-1 pathways, and distant lung injury. -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 ICAM-1 and TNF at early time points following renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly following renal ischemia. -MSH protects against both kidney and lung damage following renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury. Abstract word count: 200word count: 200