Thymopentin modulates Th1 and Th2 cytokine response and host survival in 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).


METHODS
Randomly controlled experiments.


METHODS
Two hundred sixteen Balb/c (H-2d) and 50 C3H/HeJ (H-2k) mice.


METHODS
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 remaining 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 simultaneous gavage with 1 x 10(9) Escherichia coli and the other 20 mice underwent a sham burn. The 20 nontransfused mice also received a 20% burn plus bacterial gavage. In all animals Thy was administered for 15 days. Three control groups (n = 20 each) entered the same protocol design, but they did not receive Thy. In the second study 96 animals were randomized to six groups (n = 16 each) according to the above experimental 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 plasma levels.


RESULTS
The highest mortality (70%) occurred when T was combined with BG. Thy significantly reduced mortality in both groups that 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 production of IL-2.


CONCLUSIONS
The protective effect of Thy in this experimental model may be mediated by modulation of cytokine release.
Braga
M
M
Department of Surgery, Raffaele Hospital, University of Milan, Italy.
Gianotti
L
L
Gentilini
O
O
Fortis
C
C
Consogno
G
G
Di Carlo
V
V
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001770:Blood Bactericidal Activity; D001803:Blood Transfusion; D002056:Burns / Q000276:immunology*; D005260:Female; D007376:Interleukin-2 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D016305:Thymopentin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016305:Thymopentin