Effects of interleukin-15 on suppression of rat pancreatic islets in vitro induced by proinflammatory cytokines

• Published in: Immunology letters 2003-08, Vol.88 (2), p.141-145
• Main Authors: Wallström, Johan, Andersson, Annika K., Sandler, Stellan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell Death - drug effects; Cytokine; Cytokines - pharmacology; DNA - analysis; DNA - genetics; Flow Cytometry; Glucose - metabolism; Inflammation Mediators - pharmacology; Insulin - metabolism; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-15; Interleukin-15 - genetics; Interleukin-15 - metabolism; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Oxidation-Reduction - drug effects; Pancreatic islets; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/S0165-2478(03)00073-7

The cytokine IL-15 might contribute to inflammatory processes, but also act as an inhibitor of apoptosis in different cell lines. Furthermore, it has been reported that islet cells express IL-15 after exposure to proinflammatory cytokines, which could indicate a defence reaction. We aimed in this study to investigate if IL-15 could influence cell death and/or functional impairment of rat pancreatic islets induced by in vitro exposure to a combination of cytokines (25 U/ml IL-1β+1000 U/ml IFN-γ+1000 U/ml TNF-α). The effect of IL-15 itself on the function of rat pancreatic islets was also studied. Isolated rat islets were exposed for 24 h to IL-15 at different concentrations in the presence or absence of the cytokine mixture. The cytokines caused a strong inhibition of glucose-stimulated insulin release and the glucose oxidation rates. IL-15 (0.1–10 ng/ml) could not prevent the functional suppression caused by these effects. The cytokine combination caused a decline in whole islet DNA content and a marked increase in non-viable cells analysed by propidium iodide (PI) and annexin V staining. However, there was no significant decrease in whole islet DNA content when IL-15 (0.1 or 1.0 ng/ml) was present together with the cytokine mixture. On the other hand, IL-15 failed to influence the increase in cell death after PI and annexin V staining. If anything, IL-15 alone had a slight stimulatory effect (glucose oxidation rate) on islet cells. In conclusion, we can not exclude that IL-15 might antagonize some cytokine mediated cell death in islet cells, however, IL-15 fails to counteract functional suppression induced by cytokines.