THYMOPENTIN MODULATES TH1 AND TH2 CYTOKINE RESPONSE AND HOST SURVIVALIN EXPERIMENTAL INJURY

Objective: To investigate the impact of thymopentin (Thy) on mortality and in vivo cytokine release in an animal model of gut-derived sepsis which includes different combinations of allogeneic blood transfusion (T) and burn injury plus bacterial gavage (BG). Design: Randomly cont rolled experiments. Material: Two hundred sixteen Balb/c (H-2(d)) and 50 C3H/HeJ (H-2(k)) mice. Interventions: In the first study 60 Balb/c mice were given Thy (1 mg/kg). The same day of therapy onset, 40 mice were transfused with allogeneic blood (from C3H/HeJ mice). The remaini ng 20 mice received aliquots of saline. Five days post-T, 20 of the 40 transfused mice were subjected to a 20% TBSA thermal injury and simul taneous gavage with 1 x 10(9) Escherichia coli and the other 20 mice u nderwent a sham burn. The 20 nontransfused mice also received a 20% bu rn plus bacterial gavage. In all animals Thy was administered for 15 d ays. Three control groups (n = 20 each) entered the same protocol desi gn, but they did not receive Thy. In the second study 96 animals were randomized to six groups (n = 16 each) according to the above experime ntal design. Animals were sacrificed by exsanguination after burn or 5 days post-T in nonburned mice to measure TNF-alpha, IL-2, and IL-4 pl asma levels. Results: The highest mortality (70%) occurred when T was combined with BG. Thy significantly reduced mortality in both groups t hat underwent BG, regardless of the association with T. TNF-alpha was detectable in 30% of the tested samples, IL-2 in 50%, and IL-4 in 70%. Thy significantly reduced the levels of IL-4 and increased the produc tion of IL-2. Conclusions: The protective effect of Thy in this experi mental model may be mediated by modulation of cytokine release. (C) 19 96 Academic Press, Inc.