Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons.
Increasing evidence supports a role for cytokines as chemical signals in the CNS, either under normal conditions or in the pathologic state. CNS levels of the cytokine interleukin-6 (IL-6) are known to be elevated in several diseases associated with developmental disorders and may contribute to the pathological state. To investigate the potential role of IL-6 in such disorders, neuronal effects of IL-6 were examined during development using an in vitro model system, cultured rat cerebellar granule neurons. The cultures were prepared from 8 d postnatal rat pups and exposed chronically to IL-6 (5 ng/ml) by addition to the culture medium. Neuronal effects of IL-6 were assessed by a comparison of calcium signals produced in control and IL-6 treated neurons by the glutamate receptor agonists NMDA and domoate and by K+ depolarization. IL-6 treatment significantly enhanced the response to NMDA and altered the developmental pattern of NMDA sensitivity, whereas only minor changes were observed for the response to domoate and K+. Reducing extracellular calcium and depleting intracellular stores significantly decreased the amplitude of the response to NMDA in control and IL-6 treated neurons. However, the IL-6 treated neurons were significantly more sensitive to these treatments than control neurons. These results suggest that elevated levels of IL-6 can significantly alter CNS neuron development and response to excitatory transmitters, and that IL-6 pretreatment selectively enhances the intracellular calcium responses to NMDA by altering the relative contribution of extracellular calcium influx and release of calcium from stores to the calcium signal.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D015850:Interleukin-6; D016202:N-Methylaspartate; C012301:domoic acid; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium