[Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines].
BACKGROUND
The improvement in pancreatic islet transplantation results is due to immunosuppression protocols that include, among others, low-dose tacrolimus. Both anti-inflammatory and anti-oxidant effects of tacrolimus could be useful in preventing primary rejection.


OBJECTIVE
To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation.


METHODS
Isolated rat islets were cultured in RPMI medium in the presence of IL-1 (50 UI/mL) plus IF-gamma (1000 UI/mL) and tacrolimus (5 ng/mL). The 24 h production of lipoperoxide (LPO) and nitric oxide (NO) were measured as oxidative stress markers. Determination of apoptosis markers (nucleosome content and Bcl-2) was also performed.


RESULTS
Oxidative stress (LPO 10.1+/-1.16 pmol/islet x 24; NO 19.1+/-3.28 pmol/isletx24 h) and apoptosis (nucleosome 0.24+/-0.04 UI/islet; Bcl-2 0.69+/-0.212 UI/islet) markers showed a very significant increase after cytokine stimulation (p<0.01). Both effects improved by adding tacrolimus to the medium. Protective effect was complete when lipoperoxide (1.58 pmol/isletx24 h), nitric oxide (9.81 pmol/isletx24 h) and Bcl-2 (1.37+/-0.23 UI/islet) were determined.


CONCLUSIONS
In vitro cytoprotective effect of low-dose tacrolimus on isolated rat islets decreases both oxidative stress and apoptosis markers after stimulation of pro-inflammatory mediators.
Balibrea del Castillo
José María
JM
Servicio de Cirugía General y Digestiva, Hospital Universitario Germans Trias i Pujol, Departamento de Cirugía, Universidad Autónoma de Barcelona, Barcelona, Spain. balibrea@gmail.com
Arias-Díaz
Javier
J
García Martín
María Cruz
MC
Vives-Pi
Marta
M
García Pérez
Juan Carlos
JC
Cantero Cid
Ramón
R
Vara Ameigeiras
Elena
E
Balibrea Cantero
José Luis
JL
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D019610:Cytoprotection; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D016559:Tacrolimus