title: [Immunosuppression in kidney donors with rapamycin and tacrolimus. Proinflammatory cytokine expression].
abstract: The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-a, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs).
authors.affiliation: Laboratorio/Programa de Trasplante de órganos y Tejidos, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata. fcicora5@gmail.com
authors.forename: Federico
authors.initials: F
authors.lastname: Cicora
authors.forename: Javier
authors.initials: J
authors.lastname: Roberti
authors.forename: Natalia
authors.initials: N
authors.lastname: Lausada
authors.forename: Pedro
authors.initials: P
authors.lastname: González
authors.forename: Diego
authors.initials: D
authors.lastname: Guerrieri
authors.forename: Pablo
authors.initials: P
authors.lastname: Stringa
authors.forename: Clemente
authors.initials: C
authors.lastname: Raimondi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D020123:Sirolimus; D016559:Tacrolimus