title: Ganciclovir transiently attenuates murine cytomegalovirus-associated renal allograft inflammation.
abstract: BACKGROUND
  Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined.
  
  
  METHODS
  To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murine donor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining.
  
  
  RESULTS
  By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells.
  
  
  CONCLUSIONS
  In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.
authors: Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA. mshimamura@peds.uab.edu
authors: Masako
authors: M
authors: Shimamura
authors: Ute
authors: U
authors: Saunders
authors: Brian
authors: B
authors: Rha
authors: Lingling
authors: L
authors: Guo
authors: Kevin A
authors: KA
authors: Cassady
authors: James F
authors: JF
authors: George
authors: William J
authors: WJ
authors: Britt
mesh_terms: D000818:Animals; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use*; D006566:Herpesviridae Infections / Q000473:pathology / Q000517:prevention & control*; D007113:Immunity, Innate; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D016030:Kidney Transplantation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus; D014184:Transplantation, Homologous; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D015774:Ganciclovir