title: Efficacy of VIP as Treatment for Bacteria-Induced Keratitis Against Multiple Pseudomonas aeruginosa Strains.
abstract: OBJECTIVE
  Previous studies have demonstrated the efficacy of vasoactive intestinal peptide (VIP) treatment in regulating inflammation following bacterial keratitis induced by the P. aeruginosa strain 19660. However, in the current study we assessed whether disease outcome is specific to 19660 or if VIP treatment is effective against multiple P. aeruginosa strains.
  
  
  METHODS
  B6 mice received daily IP injections of VIP from -1 through 5 days post injection (p.i.). Control mice were similarly injected with PBS. Corneal infection was induced using PA 19660, PAO1 or KEI 1025. Disease response was documented and bacterial plate counts and myeloperoxidase assays were performed. Expression of select inflammatory mediators as well as enzymes associated with lipid mediator production was assessed after VIP treatment. KEI 1025 was characterized by cytotoxicity and invasion assays and then confirmed for ExoS/ExoU expression.
  
  
  RESULTS
  VIP treatment converted the susceptible response to resistant for the three P. aeruginosa strains tested. Disease response was significantly reduced with no corneal perforation. Anti-inflammatory mediators were enhanced after VIP treatment, while pro-inflammatory molecules were reduced compared to controls. Furthermore, VIP reduced inflammatory cell persistence in the cornea after infection with each of the P. aeruginosa strains.
  
  
  CONCLUSIONS
  VIP treatment is effective at ameliorating disease pathogenesis for multiple P. aeruginosa strains, both cytotoxic and invasive. This study is also the first to indicate a possible role for VIP regarding lipid mediator expression in the eye. In addition, the clinical isolate, KEI 1025, was characterized as an invasive strain. Overall, this study strengthens the preclinical development of VIP as a therapeutic agent for ocular infectious disease.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Carion
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
authors.forename: Cody R
authors.initials: CR
authors.lastname: McWhirter
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
authors.forename: Daiyajot K
authors.initials: DK
authors.lastname: Grewal
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States 2Department of Ophthalmology, Kresge Eye Institute, Detroit, Michigan, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Berger
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D058449:Intravitreal Injections; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014660:Vasoactive Intestinal Peptide