title: Dexamethasone modulation of LPS, IL-1, and TNF stimulated serum amyloid A synthesis in mice.
abstract: Three secretory products of the macrophage, interleukin 1 (IL-1), tumor necrosis factor/cachectin (TNF) and hepatocyte stimulating factor/interleukin 6 (IL-6) modulate liver protein synthesis during the acute phase response. Induction of serum amyloid A (SAA) synthesis is one of the most notable acute phase changes in liver proteins, with maximal SAA concentrations varying over a thousand-fold range in proportion to the amount of tissue injury and cell necrosis. Exogenous IL-1 and TNF induce SAA synthesis in vivo and in vitro, while exogenous IL-6 is a far less potent stimulus of in vivo SAA gene expression. Dexamethasone (DEX), a potent inhibitor of macrophage IL-1, TNF and IL-6 synthesis, was utilized to analyze the endogenous mediators of SAA synthesis in mice injected with lipopolysaccharide (LPS). DEX, although itself exhibiting the capacity to stimulate SAA synthesis to a limited extent, significantly reduced LPS induced SAA production. However, DEX did not reduce, but rather potentiated, IL-1 and TNF stimulated SAA production, indicating that these monokines do not require macrophage products to mediate their in vivo SAA inducer activity. SAA synthesis was observed in adrenalectomized mice, following administration of LPS, IL-1 and TNF, indicating that SAA induction by monokines is not secondary to corticosteroid release.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: J D
authors.initials: JD
authors.lastname: Sipe
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone