Immunosuppression in kidney donors with rapamycin and tacrolimus. Proinflammatory cytokine expression.

CICORA, FEDERICO; ROBERTI, JAVIER; LAUSADA, NATALIA; GONZÁLEZ, PEDRO; STRINGA, PABLO; RAIMONDI, CLEMENTE

MEDICINA (BUENOS AIRES)

MEDICINA (BUENOS AIRES)

Lugar: Buenos Aires; Año: 2012 vol. 72 p. 3 - 9

0025-7680

Immunosuppression in kidney donors with rapamycin and tacrolimus. Proinflammatory cytokine expression. 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 im- munosuppressive 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-α, 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 thedifferentiation of regulatory T cells (Tregs).