Effect of hyperglycemia and antioxidant on lymphocytes viability and proliferation.

MARA ROXANA RUBINSTEIN GUICHÓN; ANDRÉS ORQUEDA; MIRIAM RUTH WALD

Madrid, España

Congreso; 2nd Iberoamerican Congress on Neuroimmunomodulation; 2007

Neuroimmunomodulation International Society

Experimental literature suggests a relation between diabetes and immunosuppression. The aim of this work was to study the immune response in diabetic mice and the participation of hyperglycemia. We found a decrease in antibody production to T-dependent antigens in diabetic mice respect to controls. As hyperglycemia was demonstrated to be one of the major mechanisms involved in diabetic complications, the effects of high glucose concentrations (HG) on normal lymphocyte activity were evaluated.  HG diminished cell viability and increased apoptosis -as measured by trypan blue exclusion and Hoescht staining or propidium iodide cytometry respectively- of lymphocytes. It also inhibited proliferative responses to T and B-selective mitogens as well. High concentrations of mannitol had no effect on these parameters, thus indicating that actions of HG are not due to osmotic stress. HG also induced an increase in oxidative stress –measured by reactive oxygen species (ROS) and lipid peroxidation production- and in protein kinase C (PKC) activity, on T and B lymphocytes. Antioxidants such as C vitamin and N-acetilcysteine (NAC) completely reverted HG actions on cell viability and partially restored T and B proliferative response to mitogens. These results indicate that hyperglycemia in diabetes would interact with lymphocytes decreasing their activity and viability. In these effects an increment of oxidative stress would be responsible for cellular death, while PKC activity would be involved in proliferative actions of HG.