Sensitization of rat alveolar macrophages to enhanced TNF-alpha release by in vivo treatment with dexamethasone.
Treatment of rats with dexamethasone rapidly induced a marked weight loss which occurred within 3 days and persisted for several weeks. The cachectic state was paralleled by increased serum levels of triglycerides, albumin, and protein and a strong reduction of blood mononuclear leukocytes. In lung sections, an increased number of mononuclear giant cells was found but no bacteria, fungi, or Pneumocystis carinii organisms. Quite strikingly, alveolar macrophages from dexamethasone-treated rats, but not from control animals, were highly sensitive to LPS and released large amounts of TNF-alpha ex vivo. Also under in vivo conditions, high TNF-alpha serum concentrations were found in dexamethasone-treated but not control rats when examined 1 1/2 hr after an intravenous LPS injection. These data suggest that the glucocorticoid-induced cachexia of rats may be linked, at least in part, to readily inducible TNF-alpha release from primed macrophages.
Renz
H
H
Institute of Immunology, Philipps University, Marburg, Germany.
Henke
A
A
Hofmann
P
P
Wolff
L J
LJ
Schmidt
A
A
Rüschoff
J
J
Gemsa
D
D
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015232:Dinoprostone