title: Azithromycin treatment increases survival of high-risk corneal allotransplants.
abstract: OBJECTIVE
  To test the therapeutic efficacy of azithromycin (AZM), a macrolide antibiotic for prolonging murine "high-risk" corneal allograft survival.
  
  
  METHODS
  Fully major histocompatibility complex-mismatched corneas were transplanted from C57BL/6 donors to BALB/c recipients with suture-induced vascularized high-risk corneal beds. Recipient mice were either not treated or treated with topical AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in a masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry, and for T-cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy.
  
  
  RESULTS
  The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by the treatment. The frequency of corneas that retained complete clarity after transplantation was higher in the AZM-treated groups. Reduced graft rejection in the AZM-treated groups was not associated with a reduced allospecific T-cell response or increased frequency of regulatory T cells.
  
  
  CONCLUSIONS
  AZM is effective in prolonging survival of high-risk corneal allografts by an as yet undefined mechanism that does not seem to involve modulation of corneal neovascularization or allospecific T-cell priming.
authors: Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Carlos A
authors: CA
authors: Medina
authors: Alexander M
authors: AM
authors: Rowe
authors: Hongmin
authors: H
authors: Yun
authors: Jared E
authors: JE
authors: Knickelbein
authors: Kira L
authors: KL
authors: Lathrop
authors: Robert L
authors: RL
authors: Hendricks
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000378:metabolism; D016039:Corneal Transplantation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015704:CD4 Antigens; C476399:Cd44 protein, mouse; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018960:Hyaluronan Receptors; D017963:Azithromycin