Impaired immune responses in streptozotocin-induced type I diabetes in mice.

RUBINSTEIN R; GENARO AM; MOTTA AB; CREMASCHI GA; WALD M

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Blackwell Publishing

Año: 2008 vol. 154 p. 235 - 246

0009-9104

Diabetes is widely believed to predispose to serious infections. However, themechanisms linking diabetes and immunosuppression are not well defined.One potential mediator of the altered defence mechanisms is hyperglycaemia.It has been identified as the main factor contributing to the development ofdiseases associated with diabetes mellitus. In this study we analyse theimmune response in diabetes and the direct effect of hyperglycaemia on T andB lymphocyte reactivity. Diabetes induced an early decrease in IgG levels inthe secondary response. However, both primary responses against a T-celldependentor independent antigen were affected after 6 months of diabetesinduction. T- and B- cell proliferation was only decreased at this time. To gaininsight into the potential mechanisms involved, we evaluated the influence ofhyperglycaemia over the immune response. Pre-incubation of lymph nodeand spleen cells in a high glucose (HG) containing medium led to a significanttime- and dose-dependent decrease in T- and B-cell proliferation. This effectwas associated with the presence of HG-derived supernatants. Still viable cellsafter HG exposition were able to improve their proliferative response whencultured with the mitogen in a fresh standard medium. HG diminished cellviability, increased apoptosis and induced oxidative stress in lymphocytes.These results indicate that HG concentrations can directly affect lymphoidcell growth. An increase in oxidative stress would be implicated in this deleteriouseffect. The possibility that prolonged exposure to pathologically HGconcentrations would result in the immunosuppressive state observed indiabetes is also discussed.