title: Effect of cyclosporine, dexamethasone, and human CTLA4-Ig on production of cytokines in lymphocytes of clinically normal cats and cats undergoing renal transplantation.
abstract: OBJECTIVE
  To evaluate effects of cyclosporine, dexamethasone, and the immunosuppressive agent human CTLA4-Ig on cytokine production by feline lymphocytes in vitro and to assess patterns of cytokine production for 5 immunosuppressed renal transplant recipient cats.
  
  
  METHODS
  21 clinically normal cats and 5 immunosupressed renal transplant recipient cats.
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from clinically normal cats and stimulated with concanavalin A (Con A; 10 μg/mL) alone or Con A with cyclosporine (0.05 μg/mL), dexamethasone (1 × 10(-7)M), a combination of cyclosporine-dexamethasone, or human CTLA4-Ig (10 g/mL). Cells from transplant recipients were stimulated with Con A alone. An ELISA was performed to measure production of interferon (IFN)-γ, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, and IL-10. Proliferation of CD4+ and CD8+T cells from immunosuppressed cats were also evaluated. Pairwise comparisons were performed via a Wilcoxon signed rank test or Wilcoxon rank sum test.
  
  
  RESULTS
  Cyclosporine, dexamethasone, cyclosporine-dexamethasone combination, and CTLA4-Ig caused a significant decrease in IL-2, IFN-γ, and GM-CSF production. Cyclosporine and cyclosporine-dexamethasone, but not human CTLA4-Ig, caused a significant decrease in IL-10 production. High basal concentrations of IL-2 and IL-10 were identified in transplant recipients, and IL-10 was significantly increased in stimulated cultures. In immunosuppressed cats, there was a decrease in frequency of responders and proliferative capacity of CD4+ and CD8+T cells.
  
  
  CONCLUSIONS
  CTLA4-Ig successfully inhibited proinflammatory cytokines while sparing cytokines critical for allograft tolerance. These data may be useful for developing better strategies to prevent rejection while sparing other immune functions.
authors: Departments of Clinical Studies-Philadelphia, PA, USA. laronson@vet.upenn.edu
authors: Lillian R
authors: LR
authors: Aronson
authors: Jason S
authors: JS
authors: Stumhofer
authors: Kenneth J
authors: KJ
authors: Drobatz
authors: Christopher A
authors: CA
authors: Hunter
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D002415:Cats / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000662:veterinary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D003208:Concanavalin A; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine