Respuesta inmune en la diabetes. Efecto de la hiperglucemia y participación del estrés oxidativo

WALD, MIRIAM; RUBINSTEIN, ROXANA

Anales de la Fundación Alberto J. Roemmers

La Prensa Médica Argentina

Lugar: Ciudad de Buenos Aires; Año: 2008 vol. XIX p. 561 - 570

 Diabetes is widely believe to predispose to serious infections.  Experimental clinical literature supports an association between diabetes and infection. Since hyperglycemia has been identified as the main factor contributing to the development of diseases associated to diabetes mellitus, the aim of the present study was to examine the effects of hyperglycemia on normal immune response.  We studied  the direct effects of elevated extracellular glucose concentration on lymphoid cells.  For this purpose “in vitro” experiments were performed by culturing murine T and B lymphocytes in the absence or presence of high concentrations of glucose. In this conditions T and B lymphocyte viability, proliferation, protein kinase C (PKC) activity and oxidative stress production were measured to mimick the direct action of hyperglycemia on the main cells of the immune system. We found  that 24 h exposure of isolated lymphocytes to high glucose specifically reduced T and B cell proliferation and increase T and B cell apoptosis and necrosis.  The effect of high glucose associated with hypertonic glucose was not observed with similar osmotic concentrations of mannitol, suggesting that glucose may have a suppressive effect on lymphocyte proliferation and viability that is independent of osmolarity.  In addition, the present results suggest that the effect of high glucose is dose and time dependent. The mechanisms by which high glucose inhibits cellular proliferation are not clear, but include PKC, since high glucose impaired the mitogen induced increase in PKC activity. High glucose leads to an increase in oxidative stress which in turn may activate death pathways implicated in cell necrosis and apoptosis. Antioxidants like vitamin C and  NAC at doses inhibiting high glucose induced oxidative stress increment abolish high glucose induced T and B cell apoptosis and reduction in T and B proliferation. Although extrapolation to in vivo conditions must be handled with caution, it can be suggested that prolonged exposure to pathologically high glucose concentrations results in a decrease in T and B cell proliferation and an increased lymphocyte death that may represent an important factor contributing to the immunosupression state observed in diabetes.