Physiological and pathological roles of interleukin-6 in the central nervous system (original) (raw)
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Interleukin-6, a major cytokine in the central nervous system
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Interleukin-6 (IL-6) is a cytokine originally identified almost 30 years ago as a B-cell differentiation factor, capable of inducing the maturation of B cells into antibody-producing cells. As with many other cytokines, it was soon realized that IL-6 was not a factor only involved in the immune response, but with many critical roles in major physiological systems including the nervous system. IL-6 is now known to participate in neurogenesis (influencing both neurons and glial cells), and in the response of mature neurons and glial cells in normal conditions and following a wide arrange of injury models. In many respects, IL-6 behaves in a neurotrophin-like fashion, and seemingly makes understandable why the cytokine family that it belongs to is known as neuropoietins. Its expression is affected in several of the main brain diseases, and animal models strongly suggest that IL-6 could have a role in the observed neuropathology and that therefore it is a clear target of strategic therapies.
Functional repertoire of interleukin-6 in the central nervous system – a review
In an aging society with dementia imposing an increasing threat to higher brain cognitive functions, understanding the molecular and cellular events of adult neurogenesis is imperative. Interleukin-6 (IL-6), along with its agonistic acting soluble receptor sIL-6R (the combined proteins are also known as Hyper-IL-6), is a promising cytokine that can support neurogenesis under conditions of neurodegeneration when neuron replacement is needed. In contrast to the previously reported gliogenic effects of activation of the IL-6–signal transducer and activator of transcription 3 (STAT3) axis, this review summarizes recent studies showing that IL-6 activation can be neurogenic and has potential therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson's disease.
IL-6 Regulation of Synaptic Function in the CNS
Neuropharmacology, 2014
A growing body of evidence supports a role for glial-produced neuroimmune factors, including the cytokine IL-6, in CNS physiology and pathology. CNS expression of IL-6 has been documented in the normal CNS at low levels and at elevated levels in several neurodegenerative or psychiatric disease states as well as in CNS infection and injury. The altered CNS function associated with these conditions raises the possibility that IL-6 has neuronal or synaptic actions. Studies in in vitro and in vivo models confirmed this possibility and showed that IL-6 can regulate a number of important neuronal and synaptic functions including synaptic transmission and synaptic plasticity, an important cellular mechanism of memory and learning. Behavioral studies in animal models provided further evidence of an important role for IL-6 as a regulator of CNS pathways that are critical to cognitive function. This review summarizes studies that have lead to our current state of knowledge. In spite of the pr...
Role of IL-6 in the regulation of neuronal development, survival and function
Cytokine
The pleiotropic cytokine interleukin-6 (IL-6) is emerging as a molecule with both beneficial and destructive potentials. It can exert opposing actions triggering either neuron survival after injury or causing neurodegeneration and cell death in neurodegenerative or neuropathic disorders. Importantly, neurons respond differently to IL-6 and this critically depends on their environment and whether they are located in the peripheral or the central nervous system. In addition to its hub regulator role in inflammation, IL-6 is recently emerging as an important regulator of neuron function in health and disease, offering exciting possibilities for more mechanistic insight into the pathogenesis of mental, neurodegenerative and pain disorders and for developing novel therapies for diseases with neuroimmune and neurogenic pathogenic components.
Interleukin-6: a cytokine with a pleiotropic role in the neuroimmunoendocrine network
Open …, 2010
Interleukin 6 (IL-6) is a typical pleiotropic cytokine that modulates a variety of physiological events in vertebrates, including cell proliferation, differentiation, survival, and apoptosis, among other functions. IL-6 plays roles in the immune, the endocrine, the nervous, and the hematopoietic systems, in bone metabolism, regulation of blood pressure and inflammation. IL-6 exerts its effects on different tissues and organ systems. Many cell types are reported to produce IL-6: T cells, B cells, polymorphonuclear cells, eosinophils, monocyte/macrophages, mast cells, dendritic cells, chondrocytes, osteoblasts, endothelial cells, skeletal and smooth muscle cells, islet cells, thyroid cells, fibroblasts, mesangial cells, keratinocytes, microglial cells, astrocytes, oligodendrocytes, adipose tissue and certain tumor cells. Here, we review the participation of the IL-6 in the neuroimmunoendocrine network. The specific targeting of the IL-6 pathway can be a promising new approach for the treatment and prevention of neurodegenerative disorders in humans as well as improving the autoinflammatory process both systemically and locally.
Journal of Neuroimmunology, 1995
In this study, we investigated the capacity of murine cortical neurons to express interleukin-6 (IL-6) mRNA and protein in culture. Using in situ hybridization techniques, IL-6 mRNA was localized to neuronal cells in these cultures. Moreover, IL-6 mRNA expression as measured by in situ and PCR was shown to be upregulated by the proinflammatory cytokines interleukin-1 /3 (IL-I p> and tumor necrosis factor-a (TNF-(Y). This was consistent with the dose and time-dependent increases in IL-6 secreted protein observed from cultures stimulated with IL-l /3 and TNF-a. Taken together, the data suggest that neurons are capable of participating more directly in the CNS cytokine network than previously thought and may play an important role in the inflammatory response activities in the brain. Keywords: Cortical neuron; Interleukin-18; Tumor necrosis factor-a; Interleukin-6 0165-5728/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDI 0165-5728(95)00134-4 114 GE.
European Journal of Neuroscience, 1995
Growing evidence suggests that aberrant production of inflammatory cytokines within the central nervous system (CNS) contributes to the development of pathological conditions. To test the cause—effect relationship between the overproduction of interleukin-6 (IL-6) in the CNS and the onset of neuropathological changes, we have generated transgenic mice in which human IL-6 expression has been targeted to the neurons by using the rat neuron-specific enolase promoter. These mice develop reactive astrocytosis and an increase in ramified microglial cells but do not show histological or behavioural signs of neuron damage at the light microscope level. We thus conclude that a constant release of human IL-6 by neuronal subpopulations in mice is sufficient to activate cells potentially capable of modulating the local immune response, but at the same time is compatible with normal neuron functions.