PMID- 8679228
OWN - NLM
STAT- MEDLINE
DCOM- 19960820
LR  - 20201209
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 15
IP  - 1
DP  - 1996 Jul
TI  - Glucocorticoid effects in an endotoxin-induced rat pulmonary inflammation model: 
      differential effects on neutrophil influx, integrin expression, and inflammatory 
      mediators.
PG  - 97-106
AB  - 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.
FAU - O'Leary, E C
AU  - O'Leary EC
AD  - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Marder, P
AU  - Marder P
FAU - Zuckerman, S H
AU  - Zuckerman SH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antigens, CD1)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Endotoxins)
RN  - 0 (Glucocorticoids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Integrins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Monokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126880-86-2 (L-Selectin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
SB  - IM
MH  - Animals
MH  - Antibody Specificity
MH  - Antigens, CD1/metabolism
MH  - Body Weight/drug effects
MH  - Bronchoalveolar Lavage Fluid/chemistry/cytology
MH  - Cell Adhesion Molecules/analysis/drug effects
MH  - Chemokine CXCL2
MH  - Dexamethasone/*pharmacology
MH  - Disease Models, Animal
MH  - Endotoxins
MH  - Flow Cytometry
MH  - Glucocorticoids/*pharmacology
MH  - Inflammation Mediators/*analysis
MH  - Integrins/*biosynthesis
MH  - Kinetics
MH  - L-Selectin/immunology/metabolism
MH  - Leukocyte Count
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages, Alveolar/chemistry/drug effects/immunology
MH  - Male
MH  - Monokines/biosynthesis/drug effects
MH  - Neutrophils/drug effects/*immunology
MH  - Pancreatic Elastase/antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Respiratory Distress Syndrome/chemically induced/pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis/drug effects
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - 10.1165/ajrcmb.15.1.8679228 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 1996 Jul;15(1):97-106. doi: 
      10.1165/ajrcmb.15.1.8679228.