Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy.
Patients with acute kidney injury frequently have pulmonary complications. Similarly ischemic acute kidney injury or bilateral nephrectomy in rodents causes lung injury characterized by pulmonary edema, increased pulmonary capillary leak and interstitial leukocyte infiltration. Interleukin-6 is a pro-inflammatory cytokine that is increased in the serum of patients with acute kidney injury and predicts mortality. Here we found that lung neutrophil infiltration, myeloperoxidase activity, the neutrophil chemokines KC and MIP-2 and capillary leak all increased within 4 h following acute kidney injury in wild-type mice. These pathologic factors were reduced in interleukin-6-deficient mice following acute kidney injury or bilateral nephrectomy. The lungs of mutant mice had reduced KC but MIP-2 was similar to that of wild type mice. Wild-type mice, treated with an interleukin-6 inactivating antibody, had decreased lung myeloperoxidase activity and KC levels following acute kidney injury. Our study shows that interleukin-6 contributes to lung injury following acute kidney injury.
Klein
Christina L
CL
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Hoke
Tom S
TS
Fang
Wen-Feng
WF
Altmann
Christopher J
CJ
Douglas
Ivor S
IS
Faubel
Sarah
S
D058186:Acute Kidney Injury / Q000150:complications* / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability; D018925:Chemokines / Q000032:analysis; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D007511:Ischemia / Q000150:complications*; D008171:Lung Diseases / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D009392:Nephrectomy / Q000009:adverse effects*; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism
D018925:Chemokines; D015850:Interleukin-6; D009195:Peroxidase