Ulinastatin alone does not reduce caspase 3-mediated apoptosis in protease-positive Aeromonas hydrophilia-induced sepsis.

OBJECTIVE

To evaluate the effect of ulinastatin, a protease inhibitor, on survival and apoptosis in protease-positive Aeromonas hydrophilia (PPAH)-induced sepsis.

METHODS

Thirty mice were randomly allocated to receive intraperitoneal injection of either phosphate buffered saline (PBS) (control mice, n = 10) or PPAH (PPAH mice, n = 20). After 30 minutes, control mice received an additional intraperitoneal PBS injection, 10 PPAH mice received intraperitoneal PBS injection (non-treated PPAH mice), and the remaining 10 PPAH mice received an intraperitoneal injection of ulinastatin (ulinastatin-treated PPAH mice).

RESULTS

Survival at 24 hours was 100% in control mice, and 35% (p < 0.05) in PPAH mice; the survival rate in non-treated and ulinastatin-treated PPAH mice were 30% and 40% (p > 0.05), respectively. The thymus weight (mg) decreased significantly in PPAH mice (51.1 +/- 14.9) compared to control mice (69.7 +/- 14.4; p < 0.001); there was no difference between ulinastatin-treated (52 +/- 13.9; p > 0.05) and non-treated PPAH mice (50.4 +/- 16). The thymus gland cell count reduced significantly in PPAH mice (8.1 +/- 4.7 x 10(7)) compared to control mice (12.8 +/- 6.6 x 10(7); p < 0.01), and immunofluorescence analysis demonstrated that the reduced cells were mostly CD4+ CD8+, in contrast to the increase in CD4+ CD8- cells. There was no difference in cell count between ulinastatin-treated (8.7 +/- 4.9 x 10(7)) and non-treated PPAH mice (7.4 +/- 4.6 x 10(7); p > 0.05). Caspase 3-mediated apoptosis was not detectable in control mice in contrast to the pronounced manifestation in PPAH mice.

CONCLUSIONS

PPAH-induced sepsis has a high mortality that is related to lymphocyte apoptosis. Ulinastatin alone does not significantly reduce caspase 3-mediated lymphocyte apoptosis.