title: Effects of the immunosuppressant FK506 on a penetrating keratoplasty rejection model in the rat.
abstract: OBJECTIVE
  The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model.
  
  
  METHODS
  Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry.
  
  
  RESULTS
  The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas.
  
  
  CONCLUSIONS
  These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.
authors.affiliation: Department of Ophthalmology, Escola Paulista de Medicina, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Nishi
authors.forename: C P
authors.initials: CP
authors.lastname: Herbort
authors.forename: M
authors.initials: M
authors.lastname: Matsubara
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Nieda
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007124:Immunoenzyme Techniques; D015948:Keratoplasty, Penetrating / Q000276:immunology* / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
chemical_list: D000949:Histocompatibility Antigens Class II; D015375:Receptors, Interleukin-2; D016559:Tacrolimus