Anti-inflammatory effect of pre-elafin in lipopolysaccharide-induced acute lung inflammation.
The aim of the present study was to evaluate the anti-inflammatory activity of pre-elafin, an elastase-specific inhibitor, in lipopolysaccharide (LPS)-induced acute lung inflammation. C57BL/6 mice were pre-treated intranasally with recombinant human pre-elafin or vehicle only. One hour later, they were instilled intranasally with LPS (2 microg/mouse). Animals were sacrificed 6 hours after LPS instillation and bronchoalveolar lavage (BAL) was performed with three 1-ml aliquots of saline. LPS induced a lung inflammation characterised by a 100-fold increase in BAL neutrophils compared to control animals (265.8 +/- 54.5 x 10(3) and 2.4 +/- 1.3 x 10(3) neutrophils/ml, respectively). Pre-elafin dose-dependently reduced the neutrophil influx in the lung alveolar spaces by up to 84%. No elastase activity was detectable in all BAL fluids tested. Pre-elafin also reduced significantly LPS-induced gelatinase activity, as shown by zymography, and BAL macrophage inflammatory protein-2 (MIP-2) and KC levels, two potent neutrophil attractants and activators. Moreover, pre-elafin also significantly reduced mRNA levels of the three members of the IL-1 ligand family, namely IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1Ra), type II IL-1 receptor, and TNFalpha as assessed in whole lung tissue by RNase protection assay. Thus, pre-elafin may be considered as a potent anti-inflammatory mediator.
Vachon
Eric
E
Centre de Recherche, Hĵpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Quebec City, Canada.
Bourbonnais
Yves
Y
Bingle
Colin D
CD
Rowe
Sarah J
SJ
Janelle
Marie France
MF
Tremblay
Guy M
GM
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000187:drug effects; D004792:Enzyme Precursors / Q000494:pharmacology*; D005260:Female; D018093:Gelatinases / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D010196:Pancreatic Elastase / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004792:Enzyme Precursors; D008070:Lipopolysaccharides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011993:Recombinant Fusion Proteins; D010196:Pancreatic Elastase; D018093:Gelatinases