Transforming growth factor beta contributes to lung leak in rats given interleukin-1 intratracheally.
Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1alpha (rhIL-1alpha) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor beta (TGFbeta) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGFbeta (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGFbeta contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.
Hybertson
Brooks M
BM
Webb-Waring Institute for Cancer, Aging, and Antioxidant Research, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Brooks.Hybertson@UCHSC.edu
Jepson
Eric K
EK
Allard
Jenny D
JD
Cho
Okyong J
OJ
Lee
Young M
YM
Huddleston
Jennifer R
JR
Weinman
Jason P
JP
Oliva
Anthony M
AM
Repine
John E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D009504:Neutrophils; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009195:Peroxidase; D010100:Oxygen