Comparative effects of betamethasone, cyclosporin and nedocromil sodium in acute pulmonary inflammation and metalloproteinase activities in bronchoalveolar lavage fluid from mice exposed to lipopolysaccharide.
Matrix metalloproteinases (MMPs) are particularly potent in degrading basement membrane collagen associated with lung injury in inflammatory processes. We have investigated the effects of betamethasone, cyclosporin, and nedocromil on MMP2 and MMP9 activities, on TNF-alpha and IL-10 release, as well as on the recruitment of inflammatory cells in the bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. When mice were pretreated with betamethasone (5 mg/kg, po), MMP2 and MMP9 activities, TNF-alpha in BAL fluids, and the enhanced neutrophil number of LPS-exposed mice were reduced, whereas the level of IL-10 was increased. Pretreatment of mice with cyclosporin (10 mg/kg, po) did not significantly reduce MMP activities, but cyclosporin inhibited neutrophil recruitment, inhibited increase TNF- alpha and inhibited IL-10 decrease. Nedocromil sodium (30 mg/kg, ip) had no influence on the LPS-induced MMP activities, on neutrophil recruitment, or on IL-10 level, but this drug elicited a significant inhibition of TNF- alpha level. These results showed that treatment with the antiinflammatory drugs cyclosporin and nedocromil sodium did not lead to reduction of MMP release. However, since betamethasone reduced the LPS-induced pulmonary inflammation and production of MMPs, these results suggest that corticosteroids may decrease tissue remodelling associated with acute lung injury.
INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2 Avenue du Prof. Léon Bernard, Rennes, 35043, France.
M
M
Corbel
V
V
Lagente
N
N
Théret
N
N
Germain
B
B
Clément
E
E
Boichot
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001485:Basement Membrane / Q000201:enzymology; D001623:Betamethasone / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology / Q000503:physiopathology; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D017835:Nedocromil / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D017835:Nedocromil; D016572:Cyclosporine; D001623:Betamethasone; D008666:Metalloendopeptidases