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.
Su
Bai-Horng
BH
Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan.
Chiu
Hsiao-Yu
HY
Soga
Taketomo
T
Lin
Kuo-Juei
KJ
Hsu
Chao-Tien
CT
D016980:Aeromonas hydrophila / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006023:Glycoproteins / Q000494:pharmacology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D008206:Lymphatic Diseases / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D018805:Sepsis / Q000188:drug therapy*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D006023:Glycoproteins; D014361:Trypsin Inhibitors; D053148:Caspase 3; C028665:urinastatin