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.
Thier
M
M
Institute of Neuropathology, Technical University (RWTH), Aachen, Germany.
März
P
P
Otten
U
U
Weis
J
J
Rose-John
S
S
D000818:Animals; D000831:Animals, Newborn; D019898:Autocrine Communication / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000378:metabolism*
D020934:Ciliary Neurotrophic Factor; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D020932:Nerve Growth Factor