Sympathetic neurons can produce and respond to interleukin 6

Abstract

Neuronal expression of cytokines is an area of active investigation in the contexts of development, disease, and normal neural function. Although cultured rat sympathetic neurons respond very weakly to exogenous interleukin 6 (IL-6), we find that addition of soluble IL-6 receptor (sIL-6R) and IL-6 enhances neuronal survival in the absence of nerve growth factor. Neutralizing monoclonal antibodies against IL-6 block these effects. Addition of IL-6 and sIL-6R also induces a subset of neuropeptide and transmitter synthetic enzyme mRNAs identical to that demonstrated for leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Both of these effects are duplicated by addition of a highly active fusion protein of sIL-6R and IL-6, covalently linked by a f lexible peptide chain, which is designated H-IL-6. In addition, we show that sympathetic neurons produce IL-6. In situ hybridization indicates a neuronal localization of IL-6 mRNA in superior cervical ganglia, and bioactive IL-6 protein is detected in ganglion culture supernatants. Interestingly, the IL-6 produced by sympathetic neurons does not lead to survival of these cells in culture unless sIL-6R is added. Thus, sympathetic neurons can produce IL-6 and may respond to it in an autocrine͞paracrine manner if sIL-6R is present. Moreover, the prior findings of sIL-6R in serum and inf lammatory f luids now have added interest in the context of neuroimmune interactions.

Activation of Antigen-Specific CD4+ Th2 Cells and B Cells In Vivo Increases Norepinephrine Release in the Spleen and Bone Marrow

“…Recently, this study was further supported by the findings that cytokine receptors are present on various types of peripheral nerves, including sensory nerves (38), sympathetic nerves (39,40), sympathetic ganglia (41,42), and vagal nerve paraganglia (4), all of which are found outside the CNS. Therefore, the presence of cytokine receptors on peripheral nerves provides a potential mechanism by which local immune cell-derived cytokines produced in the periphery may transmit signals to the CNS or the peripheral nerve directly (see model in Fig.…”

Proinflammatory Cytokine, Chemokine, and Cellular Adhesion Molecule Expression during the Acute Phase of Experimental Brain Abscess Development

“…However, the amount of IL-6R on astrocytes is not sufficient by itself to deliver an activation signal, and requires the presence of a soluble form of the IL-6R generated by shedding of the membrane-bound receptor or by mRNA alternative splicing. 25,48 Interestingly, astrocytes and sympathetic neurons can produce IL-6 and may respond to it in an autocrine/paracrine manner if sIL-6R is present, 25,48,49 a mechanism for amplifying IL-6 expression in the CNS. We are actively investigating proinflammatory cytokine receptor expression to identify which cell populations are competent to respond to the mediators detected in early brain abscess lesions.…”

Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display

“…Furthermore, it was shown that the sIL-6-R strongly sensitizes IL-6-responsive target cells (59). transsignaling cell types that are exclusively responsive to IL-6/IL-6-R but not to IL-6 alone include hematopoietic progenitor cells (61), endothelial cells (67), osteoclasts (77), smooth muscle cells (32), and neuronal cells (39,40).…”