Adenosine-induced neuroprotection: involvement of glia cells and cytokines

Adenosine is released during pathological conditions and has significant neuroprotective effects mainly by stimulating adenosine A1 receptors in neurons. These neuroprotective effects are increased following upregulation of adenosine A1 receptors. Much research has been performed to enhance the neuroprotective effects of adenosine experimentally. Since direct interference with the adenosinergic system causes side effects, it would be preferable to find ways to increase the neuroprotective effects of adenosine indirectly, for example by finding factors that increase adenosine A1 receptor expression. Like adenosine, the proinflammatory cytokine interleukin-6 (IL-6) is released during pathological conditions and IL-6 is also known to reduce neuronal damage and mortality. In contrast to adenosine, however, little is known so far regarding the mechanism of IL-6 mediated neuroprotection. Recent findings in vitro have shown that IL-6 is being released by cultured astrocytes after adenosine receptor stimulation [76, 191]. Furthermore, it has been shown that stimulation with IL-6 increases the expression of adenosine A1 receptors in nervous tissue, which implies that the neuroprotective effect of IL-6 might partially be due to upregulation of adenosine A1 receptors [23]. From these findings we propose a model for inter-actions between the adenosinergic system and IL-6 (Figure 1.6). The aim of the current thesis is to further investigate the interactions between the adenosinergic system and IL-6 and to check whether IL-6 has an effect on adenosine A1 receptor expression in pathological conditions.