title: Immunomodulatory effect of gatifloxacin on mouse peritoneal macrophages in vitro and in models of endotoxin-induced rat conjunctivitis and rabbit bacterial keratitis.
abstract: OBJECTIVE
  To determine the anti-inflammatory activity of gatifloxacin in ophthalmic use.
  
  
  METHODS
  The following 3 experiments were carried out. (1) Rabbits were inoculated intracorneally with methicillin-resistant Staphylococcus aureus and topically treated with gatifloxacin or levofloxacin. The severity of infection and viable bacterial count were assessed. (2) Thioglycollate-elicited mouse peritoneal macrophages were stimulated by Pseudomonas lipopolysaccharides (LPS) in the presence of graded concentrations of fluoroquinolones, and macrophage-derived tumor necrosis factor alpha (TNF-alpha) was assessed. (3) The effects of fluoroquinolones on TNF-alpha production were compared in an LPS-induced rat conjunctivitis model.
  
  
  RESULTS
  In the rabbit keratitis model, the ocular inflammation was significantly reduced by gatifloxacin as compared to levofloxacin but there was no significant difference between the groups in the number of viable bacteria. Gatifloxacin and levofloxacin suppressed TNF-alpha production in mouse macrophages in a concentration-dependent manner, and the effect of gatifloxacin was more potent than that of levofloxacin. Moxifloxacin exhibited no effect in this condition. In the rat conjunctivitis model, the tissue TNF-alpha level was significantly reduced only in the group instilled with gatifloxacin ophthalmic solution.
  
  
  CONCLUSIONS
  These results indicate that gatifloxacin has not only antibacterial activity but an anti-inflammatory action caused by at least inhibiting TNF-alpha production at the doses used in topical ophthalmic therapy.
authors.affiliation: Research Laboratories, Senju Pharmaceutical Co., Ltd., Kobe, Japan. tmwada@senju.co.jp
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Wada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kida
authors.forename: Takateru
authors.initials: T
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Tokushige
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Naka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakaki
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D003231:Conjunctivitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004731:Endotoxins; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D007155:Immunologic Factors / Q000494:pharmacology*; D007634:Keratitis / Q000382:microbiology* / Q000473:pathology*; D064704:Levofloxacin; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008809:Mice, Inbred C3H; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D004731:Endotoxins; D024841:Fluoroquinolones; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin