Interleukin-6 ( IL-6) and its soluble receptor support survival of sensory neurons.
The cytokine interleukin-6 ( IL-6) has multiple functions in the immune and hematopoietic systems. IL-6 is related to ciliary neurotrophic factor ( CNTF), a trophic factor for motoneurons, sensory dorsal root ganglion (DRG) neurons, and other neuronal subpopulations. Both act via related receptor complexes, consisting of one ligand-specific alpha-receptor subunit ( IL-6R and CNTFR, respectively) and two signal-transducing receptor components. Even though IL-6 is expressed by neurons and glia, the functions of IL-6 in the nervous system are poorly understood. Here, we report that exogenous human IL-6 promotes the survival of dissociated newborn rat DRG neurons in vitro if supplemented with soluble human IL-6-alpha-receptor. The dosages of human IL-6 and soluble human IL-6R necessary to achieve neurotrophic effects could be reduced markedly by linking ligand and alpha-receptor component in a designer cytokine. Furthermore, we show that newborn rat DRG neurons express and secrete bioactive IL-6. Endogenously secreted IL-6 does not enhance survival of these neurons in vitro, suggesting that DRG neurons do not sufficiently express cell surface IL-6R. Exogenously added soluble rat IL-6R rendered DRG neurons responsive to secreted IL-6. Our results indicate an autocrine function of IL-6 in DRG neuron survival which depends on membrane- bound or soluble IL-6R as a neurotrophic cofactor.[1]References
- Interleukin-6 (IL-6) and its soluble receptor support survival of sensory neurons. Thier, M., März, P., Otten, U., Weis, J., Rose-John, S. J. Neurosci. Res. (1999) [Pubmed]
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