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Journal of Neuroscience, Vol 15, 6688-6699, Copyright © 1995 by Society for Neuroscience
Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons
Z Qiu, KL Parsons and DL Gruol
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
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.
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