P.101: Thalidomide as a potent immunomodulator in a donor brain death experimental model.

Background: The brain death in the donor has been recognized as an important risk factor for the survival of liver transplant recipients. It is associated with intense immune response leading hepatocyte dysfunction, and therefore significantly decreasing the viability of transplanted livers. In this setting, thalidomide, due to its potent anti-inflammatory and immunomodulatory properties, may represent an alternative strategy of liver donor management. Thus, we sought to investigate the effects of thalidomide on liver in an experimental model of brain death. Methods: Brain death induction was induced using inbred Lewis (LEW) rats by inflating a Fogarty catheter placed in the epidural space. Rats were divided into 2 groups: Brain Death (BD), rats submitted to brain death (n=8); BD + Thalid, BD rats receiving Thalidomide (200 mg/Kg) by gavage immediately after brain death (n=8). Rats were monitored for 6h after BD and parameters were analyzed. Besides serum biochemistry (AST and ALT) and immunohistochemistry (M1 macrophages) analysis, we also analyzed the mRNA expression (RT-PCR) and protein levels (Multiplex/Luminex) of cytokines TNF-α and IL-1β in liver samples. Results: Thalidomide treatment resulted in a significant reduction of serum levels of AST and ALT (349±27 vs. 231±32 U/L; 233±41 vs. 83±5 U/L, respectively; P<0.05). Moreover, local M1 macrophage infiltration was significantly reduced by thalidomide treatment (14.2±1.3 vs. 9.3±2.3 cells mm2, P<0.05). Thalidomide treatment also significantly attenuated cytokines evaluated either at the mRNA expression and protein levels in liver tissues: TNF-α (2.2±0.1 vs. 1.3±0.3 relative expression; 478.8±109.5 vs. 33.3±6.7 pg/mL, respectively; P<0.05) and IL-1β (2.9±0.2 vs. 2.1±0.1 relative expression; 247.0±29.8 vs. 30.0±1.7 pg/mL, respectively; P<0.05). Conclusions: The negative impact of immunological response in this brain death model was overcome by the potent anti-inflammatory and immunomodulatory properties of thalidomide, promoting liver protection.