Cytokine-induced neutrophil chemoattractant is necessary for interleukin-1-induced lung leak in rats.
Because interleukin-1 (IL-1) is not a potent chemoattractant intrinsically, our goal was to determine whether cytokine-induced neutrophil chemoattractant (CINC) mediates neutrophil accumulation and leak that occur in lungs of rats given IL-1 intratracheally. We found that rats given IL-1 intratracheally had increased lung lavage CINC concentrations, lung myeloperoxidase (MPO) activity, lung lavage neutrophil numbers, and lung leak compared with saline-treated control rats. In parallel, rats given increasing doses of anti-CINC antibody along with IL-1 intratracheally had progressively decreased lung lavage CINC concentrations, lung lavage neutrophil numbers, and lung leak, but the same lung MPO activity, as did rats given only IL-1 intratracheally. In addition, lavage CINC concentrations correlated with lavage neutrophil numbers in rats. Because CINC is a chemoattractant in vitro and because anti-CINC antibody decreased lung leak induced by IL-1, CINC was then given alone intratracheally. Rats given only CINC intratracheally had the same lung MPO activity, lung lavage neutrophil numbers, and lung leak as did saline-treated control rats. These observations suggest that instilling IL-1 intratracheally induces lung leak via a CINC-dependent pathway but that administering CINC alone in concentrations exceeding the levels measured in lung lavages from IL-1-treated rats is not sufficient to cause lung neutrophil accumulation and lung leak.
Koh
Y
Y
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262, USA.
Hybertson
B M
BM
Jepson
E K
EK
Cho
O J
OJ
Repine
J E
JE
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism / Q000502:physiology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007278:Injections, Spinal; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D009195:Peroxidase