Ulinastatin Alone Does Not Reduce Caspase 3-mediated Apoptosis in Protease-positive Aeromonas hydrophilia-induced Sepsis

Background/purposeTo evaluate the effect of ulinastatin, a protease inhibitor, on survival and apoptosis in protease-positive Aeromonas hydrophilia (PPAH)-induced sepsis.MethodsThirty 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).ResultsSurvival 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 × 107) compared to control mice (12.8 ± 6.6 × 107; 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 × 107) and non-treated PPAH mice (7.4 ± 4.6 × 107; p > 0.05). Caspase 3-mediated apoptosis was not detectable in control mice in contrast to the pronounced manifestation in PPAH mice.ConclusionPPAH-induced sepsis has a high mortality that is related to lymphocyte apoptosis. Ulinastatin alone does not significantly reduce caspase 3-mediated lymphocyte apoptosis. [J Formos Med Assoc 2007; 106(2):97-104]