CEREBELLAR GRANULE NEURONS DEVELOP ELEVATED CALCIUM RESPONSES WHEN TREATED WITH INTERLEUKIN-6 IN CULTURE

In humans, elevated levels of cytokines are associated with several di seases (including HIV infection and Down Syndrome) that result in deve lopmental abnormalities. Overexpression of interleukin-6 (IL-6) in the central nervous system has been shown to cause extensive neuronal abn ormality in mice that becomes more evident with maturation. However, i t is difficult to separate direct effects of IL-6 on the developing ne urons of an intact animal from indirect effects involving effects on o ther cell types that possess cytokine receptors, such as microglia and astrocytes. We have found that IL-6 treatment of rat cerebellar granu le neurons developing in the absence of other cell types in culture re sults in the persistence of large, depolarization or neurotransmitter- induced calcium transients that are normally observed only in immature neurons. The cause of this appears to be the persistence of a calcium -induced calcium release (CICR) component of the calcium response to s timulation. This basic abnormality in neuronal development may contrib ute to the developmental abnormalities associated with human syndromes that involve elevated cytokine levels.