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Both adenosine and interleukin-6 (IL-6) have been implicated in the pathophysiology of, e.g., epileptic seizures, traumatic brain injury, and affective disorders. Stimulation of adenosine A2B receptors on astrocytes in vitro leads to the increased synthesis and secretion of IL-6. We investigated whether or not activation of adenosine receptors evokes an increase of IL-6 release also in vivo. 5′- N-ethylcarboxamidoadenosine, a non-specific adenosine-agonist or vehicle was administered into the striatum of freely moving mice by reverse microdialysis. A statistical significant increase of the IL-6 concentration in the perfusate was detected already 60 min after 5′- N-ethylcarboxamidoadenosine administration. IL-6 increased progressively and reached a maximum after 240 min. This effect appears to be mediated through adenosine A2B receptors since it was counteracted by the specific A2B receptor antagonist MRS1706 but not by the specific A1 receptor antagonist DPCPX. We conclude that adenosine via activation of A2B receptors evokes IL-6 release also in vivo. [ABSTRACT FROM AUTHOR]