Glucocorticoid effects in an endotoxin-induced rat pulmonary inflammation model: differential effects on neutrophil influx, integrin expression, and inflammatory mediators
| Autor: | Philip Marder, Eoin C. O'Leary, Steven H. Zuckerman |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Male ARDS Integrins Lipopolysaccharide Neutrophils Clinical Biochemistry Chemokine CXCL2 Dexamethasone Antigens CD1 Rats Sprague-Dawley chemistry.chemical_compound Leukocyte Count Antibody Specificity L-Selectin Respiratory Distress Syndrome medicine.diagnostic_test biology Pancreatic Elastase Flow Cytometry Integrin alpha M Tumor necrosis factor alpha Inflammation Mediators Bronchoalveolar Lavage Fluid Glucocorticoid medicine.drug Pulmonary and Respiratory Medicine medicine.medical_specialty CD11a Internal medicine Macrophages Alveolar medicine Animals Molecular Biology Glucocorticoids Tumor Necrosis Factor-alpha Monokines Body Weight Cell Biology medicine.disease Rats Endotoxins Disease Models Animal Kinetics Bronchoalveolar lavage Endocrinology chemistry biology.protein Cell Adhesion Molecules |
| Zdroj: | American journal of respiratory cell and molecular biology. 15(1) |
| ISSN: | 1044-1549 |
| Popis: | To understand the basis for the refractory nature of acute respiratory distress syndrome (ARDS) to glucocorticoids, the effects of dexamethasone pretreatment (DEX, 2 mg/kg, intraperitoneally) on the kinetics of airway tumor necrosis factor-alpha (TNF alpha) and macrophage inflammatory protein 2 (MIP-2) production, and polymorphonuclear leukocyte (PMN) influx after intratracheal lipopolysaccharide (LPS) (1 mg/kg) in rats were investigated. In the absence of exogenous glucocorticoids, TNF alpha and MIP-2 levels in bronchoalveolar lavage (BAL) fluid peaked at 21 and 300 ng, respectively, by 3 h. DEX pretreatment resulted in a 74% reduction in BAL TNF alpha, yet MIP-2 accumulation was unchanged. In addition, DEX reduced PMN influx at 5 h by 58.4% to 4.1 +/- 0.7 x 10(6) PMN (n = 5). DEX, however, did not mitigate the 3-fold increase in total BAL protein observed at 5 h, attributable to albumin influx. The effects of subacute DEX treatment (3.8 mg/kg per day, for 3 days) on cell-surface expression of the adhesion molecules CD11a, CD11b, and L-selectin were determined by flow cytometric analysis of peripheral blood and autologous BAL PMN. Compared with peripheral blood PMN, exudative PMN had 4-fold greater CD11b expression, no change in CD11a, and loss of L-selectin immunoreactivity 5 h after LPS challenge. The upregulation of CD11b on exudative PMN was insensitive to DEX pretreatment, which, together with a failure to suppress MIP-2 levels, provides a possible explanation for the lack of efficacy of steroids in the management of ARDS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|