Sensitization of rat alveolar macrophages to enhanced TNF-α 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-α ex vivo. Also under in vivo conditions, high TNF-α 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-α release from primed macrophages.