Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

• DOI: 10.1038/sj.npp.1301612
• Publication Date: 2007-11-07T07:41:11Z
• Authors: Knut Biber; A Pinto-Duarte; M C Wittendorp; A M Dolga; C C Fernandes; J Von Frijtag Dra...; J N Keijser; R de Vries; A P Ijzerman; J A Ribeiro; U Eisel; A M Sebastião; H W G M Boddeke
• Keywords: Male; INHIBITORY SYNAPTIC TRANSMISSION; Cell Survival; adenosine A(1) receptor; Hippocampus; RAT HIPPOCAMPUS; Mice; Radioligand Assay; 03 medical and health sciences; 0302 clinical medicine; CEREBROSPINAL-FLUID; Animals; Excitatory Amino Acid Agents; Enzyme Inhibitors; EPILEPTIC SEIZURES; Cells, Cultured; seizures; Cerebral Cortex; Mice, Knockout; Neurons; brain inflammation; MOUSE-BRAIN; Analysis of Variance; CEREBRAL-ISCHEMIA; hypoxia; Interleukin-6; Receptor, Adenosine A1; CENTRAL-NERVOUS-SYSTEM; INDUCED SEIZURES; Excitatory Postsynaptic Potentials; Embryo, Mammalian; cytokines; 3. Good health; Mice, Inbred C57BL; Autoradiography; Pentylenetetrazole; MESSENGER-RNA; excitotoxicity; DATA-ACQUISITION PROGRAM

The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A1 receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A1 receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.