title: Topical cyclosporine A inhibits subepithelial immune infiltrates but also promotes viral shedding in experimental adenovirus models.
abstract: OBJECTIVE
  To determine the effects of topical cyclosporine A (CsA), an immunomodulating T-cell inhibitor, on the formation of subepithelial immune corneal infiltrates (SEIs) and acute adenovirus replication in the NZW Rabbit Ad5 SEI and Ad5 replication models.
  
  
  METHODS
  In the Ad5 SEI model, eyes were treated topically with either 2% CsA in corn oil, 0.5% CsA in artificial tears, or their respective control vehicles 4 times daily for 14 days and then twice daily for 4 days. SEIs were graded on day 23 by masked slit-lamp examination. Using the same treatment protocol in the Ad5 replication model, rabbit eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21 postinoculation, and their tear film viral titers were determined on A549 cells.
  
  
  RESULTS
  The formation of SEIs was significantly reduced following treatment with either 2.0% or 0.5% CsA. However, 2% and 0.5% CsA significantly increased viral titers on several days, prolonged the duration of Ad5 shedding, and increased the number of Ad5-positive cultures per total during the late phase of infection (days 7-21) compared with their respective controls. The 0.5% CsA was equipotent to 2% CsA for most outcome parameters tested.
  
  
  CONCLUSIONS
  A role for topical CsA in the treatment of adenovirus ocular infections remains to be defined in large, randomized controlled clinical trials. During acute infection, reducing SEI formation is highly desirable, but enhancing viral replication may inadvertently serve to promote local epidemics. Future trials should address the important issues of optimized formulation and dose regimen and the possibility of prolonging virus shedding.
authors.affiliation: The Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. romanowskieg@upmc.edu
authors.forename: Eric G
authors.initials: EG
authors.lastname: Romanowski
authors.forename: Patricia
authors.initials: P
authors.lastname: Pless
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Yates
authors.forename: Y Jerold
authors.initials: YJ
authors.lastname: Gordon
mesh_terms: D000258:Adenovirus Infections, Human / Q000821:virology*; D000260:Adenoviruses, Human / Q000302:isolation & purification / Q000502:physiology*; D000287:Administration, Topical; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000276:immunology / Q000821:virology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007639:Keratoconjunctivitis, Infectious / Q000821:virology*; D009883:Ophthalmic Solutions; D011817:Rabbits; D013601:T-Lymphocytes / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D016572:Cyclosporine