The Journal of Neurophysiology Vol. 88 No. 1 July 2002, pp. 475-486
Copyright ©2002 by the American Physiological Society
Chronic Interleukin-6 Exposure Alters Electrophysiological
Properties and Calcium Signaling in Developing Cerebellar Purkinje
Neurons in Culture
Thomas E.
Nelson,
Christina
L.
Ur, and
Donna L.
Gruol
Department of Neuropharmacology, The Scripps Research Institute, La
Jolla, California 92037
Nelson, Thomas E.,
Christina
L. Ur, and
Donna L. Gruol.
Chronic Interleukin-6 Exposure Alters Electrophysiological
Properties and Calcium Signaling in Developing Cerebellar Purkinje
Neurons in Culture. J. Neurophysiol. 88: 475-486, 2002. The cytokine interleukin-6 (IL-6) is chronically
expressed at elevated levels within the CNS in many neurological
disorders and may contribute to the histopathological,
pathophysiological, and cognitive deficits associated with such
disorders. However, the effects of chronic IL-6 exposure on neuronal
function in the CNS are largely unknown. Therefore using intracellular
recording and calcium imaging techniques, we investigated the effects
of chronic IL-6 exposure on the physiological properties of cerebellar Purkinje neurons in primary culture. Two weeks of exposure to 1,000 units/ml (U/ml) IL-6 resulted in altered electrophysiological properties of Purkinje neurons, including a significant reduction in
action potential generation, an increase in input resistance, and an
enhanced electrical response to the ionotropic glutamate receptor
agonist, 
-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
compared with untreated neurons. Lower concentrations of IL-6 (100 and
500 U/ml) had no effects on these electrophysiological parameters.
However, neurons exposed to 500 U/ml chronic IL-6 resulted in
significantly elevated resting levels of intracellular calcium as well
as an increase in the intracellular calcium signal of Purkinje
neurons in response to AMPA, effects not observed in neurons exposed to
1,000 U/ml chronic IL-6. Morphometric analysis revealed a lack of gross
structural changes following chronic IL-6 treatment, such as in the
number, size, and extent of dendritic arborization of Purkinje neurons
in culture. Using immunohistochemistry, we found that cultured Purkinje
neurons express both the IL-6 receptor and its intracellular signaling
subunit, gp130, indicating that IL-6 may act directly on Purkinje
neurons to alter their physiological properties. The present data show
that chronic exposure to elevated levels of IL-6, such as occurs in
various neurological diseases, produces alterations in several
important physiological properties of Purkinje neurons and that these
changes occur in the absence of neuronal toxicity, damage, or death.
The results support the hypothesis that chronic IL-6 exposure can
disrupt normal CNS function and thereby contribute to the
pathophysiology associated with many neurological diseases.
