The effect of selective neutrophil elastase inhibitor on pancreatic islet yields and functions in rat with hypercytokinemia
Ono Shinichiro, Tamotsu Kuroki, Tomohiko Adachi, Taichiro Kosaka, Tatsuya Okamoto, Takayuki Tanaka, Yoshitsugu Tajima, Takashi Kanematsu, Susumu Eguchi
Ann Transplant 2011; 16(4): 99-106
Available online: 2011-12-30
Background: It is well known that to achieve insulin independence requires a high number of islets, but at present, isolation techniques can recover 50% or less of the islets present in the pancreas. Brain death is characterized by a cytokine storm that takes place in the body, and this condition reduces the islet yields and functions. In this study, we used selective neutrophil elastase inhibitor, sivelestat sodium to prevent damage to the islets for transplantation.
Material/Methods: We used three groups of rats, group1 were transfused with only saline, group 2 recieved sivelestat sodium (10 mg/kg/h) and group3 recieved a higher dose of sivelestat sodium (30 mg/kg/h). Thirty minutes after the treatment, lipopolysaccharide was injected to induce hypercytokinemia. We examined serum cytokine levels, derivatives of reactive oxygen metabolites (d-ROMs), islet yields and viability and 24hours after static incubation, the islet yields, viability, functions (insulin stimulation index and ADP/ATP ratio).
Results: The levels of serum cytokines, IL-1β, IL-6 and IFN-γ were significantly different between groups 1 and 3. The islet yields and the 24 h recovery rate of islets and insulin stimulation index were significantly higher in group 3 compared with group 1. The d-ROMs and ADP/ATP ratio were decreased by dose dependently in group 2 and 3.
Conclusions: The islet yields and functions in vitro were significantly improved by the treatment with sivelestat sodium. These experiments may lead to marginal donors, pre-treated with sivelestat sodium becoming acceptable for islet transplantation.
Keywords: Brain Death, Islet Transplantation, hypercytokinemia, sivelestat sodium