The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.
Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.
Yi
E S
ES
Department of Pathology University of California at San Diego School of Medicine 92103, USA.
Remick
D G
DG
Lim
Y
Y
Tang
W
W
Nadzienko
C E
CE
Bedoya
A
A
Yin
S
S
Ulich
T R
TR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007322:Instillation, Drug; D019272:Leukocyte Elastase / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D014132:Trachea
D000893:Anti-Inflammatory Agents; D001427:Bacterial Toxins; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; C027952:salmonella toxin; D003907:Dexamethasone; D019272:Leukocyte Elastase