PMID- 9517594
OWN - NLM
STAT- MEDLINE
DCOM- 19980407
LR  - 20181201
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 157
IP  - 3 Pt 1
DP  - 1998 Mar
TI  - Albuterol does not antagonize the inhibitory effect of dexamethasone on monocyte 
      cytokine release.
PG  - 803-9
AB  - Beta2-adrenoceptor agonists given by the inhaled route are the most effective 
      bronchodilators known, yet high doses of these drugs may be associated with an 
      increase in asthma mortality and morbidity. One theory for this paradox is that 
      chronic use of beta2-adrenoceptor agonists compromises the anti-inflammatory 
      action of glucocorticosteroids. This hypothesis derives from the ability of 
      albuterol and fenoterol to inhibit the interaction of the glucocorticosteroid 
      receptor (GR) with proinflammatory transcriptional activators acting on the 
      promoter region of certain target genes that encode cytokines such as tumor 
      necrosis factor-alpha (TNF alpha) and granulocyte/macrophage colony-stimulating 
      factor (GM-CSF). However, the functional relevance of these results has not been 
      formally investigated. We have tested the hypothesis that albuterol reduces the 
      ability of dexamethasone to inhibit the generation of TNF alpha and GM-CSF from 
      lipopolysaccharide (LPS)-stimulated human monocytes. Pretreatment of human 
      monocytes with albuterol (1 and 100 microM) for 5 and for 180 min inhibited 
      maximally TNF alpha generation by approximately 25%. However, regardless of the 
      concentration of albuterol, or the time of preincubation, the inhibitory effect 
      of dexamethasone was not significantly affected with respect to the EC50 or the 
      maximal effect produced. Qualitatively identical data were obtained when GM-CSF 
      release was used as an index of monocyte activation. We conclude that high 
      concentrations of albuterol do not compromise the ability of dexamethasone to 
      suppress the generation of TNF alpha and GM-CSF from LPS-stimulated human 
      monocytes.
FAU - Seldon, P M
AU  - Seldon PM
AD  - Thoracic Medicine, Imperial College School of Medicine at the National Heart and 
      Lung Institute, London, United Kingdom.
FAU - Stevens, D A
AU  - Stevens DA
FAU - Adcock, I M
AU  - Adcock IM
FAU - O'Connor, B J
AU  - O'Connor BJ
FAU - Barnes, P J
AU  - Barnes PJ
FAU - Giembycz, M A
AU  - Giembycz MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
MH  - Adrenergic beta-Agonists/administration & dosage/*pharmacology
MH  - Albuterol/administration & dosage/*pharmacology
MH  - Anti-Inflammatory Agents/administration & dosage/*pharmacology
MH  - Asthma/drug therapy/physiopathology
MH  - Bronchodilator Agents/administration & dosage/*pharmacology
MH  - Cells, Cultured
MH  - Cytokines/*drug effects/genetics/metabolism
MH  - Dexamethasone/administration & dosage/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Glucocorticoids/administration & dosage/*pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/drug effects/genetics
MH  - Humans
MH  - Inflammation Mediators/pharmacology
MH  - Least-Squares Analysis
MH  - Lipopolysaccharides/pharmacology
MH  - Monocytes/*drug effects/metabolism
MH  - Promoter Regions, Genetic/drug effects
MH  - Receptors, Glucocorticoid/antagonists & inhibitors
MH  - Regression Analysis
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/drug effects/genetics
EDAT- 1998/03/28 00:00
MHDA- 1998/03/28 00:01
CRDT- 1998/03/28 00:00
PHST- 1998/03/28 00:00 [pubmed]
PHST- 1998/03/28 00:01 [medline]
PHST- 1998/03/28 00:00 [entrez]
AID - 10.1164/ajrccm.157.3.9707116 [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):803-9. doi: 
      10.1164/ajrccm.157.3.9707116.