title: The serum amyloid A response to sterile silver nitrate in mice and its inhibition by dexamethasone and macrolide antibiotics.
abstract: Serum amyloid A protein (SAA) is an acute phase protein, known to be a sensitive indicator of inflammation. We have characterized the time course of the SAA response and inflammatory reaction to silver nitrate injection s.c. in mice and studied the effects of dexamethasone and macrolide antibiotics. 2% Sterile silver nitrate solution was injected s.c. into female BALB/c mice and blood collected by capillary action from the tail vein of each mouse at different time points. Hematological variables were determined, albumin by spectrophotometry and SAA and cytokines by ELISA. Animals were treated with either a single i.p. dose of dexamethasone (5-30 mg/kg) 1 h after or daily oral doses of macrolide antibiotics for 3 days. SAA concentrations after silver nitrate injection peaked at 24 h, preceded by increases in serum IL-1 beta and IL-6, associated with decreases in blood leukocytes and local tissue inflammation. Single dexamethasone treatment and daily dosing for 3 days with azithromycin, clarithromycin and roxithromycin (20-80 mg/kg p.o.), but not erythromycin (100-150 mg/kg p.o.), inhibited the increase in SAA but with varying time courses. SAA, measured continuously, is a useful marker of sterile inflammation in mice and is differentially inhibited by macrolide antibiotics.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd., Prilaz baruna Filipovica 29, HR-10000 Zagreb, Croatia. ines.z.glojnaric@gsk.com
authors.forename: Ines
authors.initials: I
authors.lastname: Glojnaric
authors.forename: Snjezana
authors.initials: S
authors.lastname: Cuzic
authors.forename: Vesna
authors.initials: V
authors.lastname: Erakovic-Haber
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology; D002452:Cell Count; D017291:Clarithromycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010976:Platelet Count; D015575:Roxithromycin / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D012835:Silver Nitrate / Q000494:pharmacology*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D018942:Macrolides; D000685:Serum Amyloid A Protein; D015575:Roxithromycin; D003907:Dexamethasone; D017963:Azithromycin; D012835:Silver Nitrate; D017291:Clarithromycin