The effect of selective neutrophil elastase inhibitor on pancreatic islet yields and functions in rat with hypercytokinemia.
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.


METHODS
We used three groups of rats, group 1 were transfused with only saline, group 2 received sivelestat sodium (10 mg/kg/h) and group 3 received 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 24 hours 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.<br />
Department of Surgery, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, Japan. shinichi0320_com@yahoo.co.jp
Ono
O
Shinichiro
Tamotsu
T
Kuroki
Tomohiko
T
Adachi
Taichiro
T
Kosaka
Tatsuya
T
Okamoto
Takayuki
T
Tanaka
Yoshitsugu
Y
Tajima
Takashi
T
Kanematsu
Susumu
S
Eguchi
D000818:Animals; D001926:Brain Death / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008297:Male; D023421:Models, Animal; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000097:blood; D013449:Sulfonamides / Q000494:pharmacology; D020858:Tissue and Organ Harvesting / Q000379:methods*
D016207:Cytokines; D053491:Proteinase Inhibitory Proteins, Secretory; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine