Interleukin-6 (IL-6): A Possible Neuromodulator Induced by Neuronal Activity

Abstract

IL-6 and its receptor(s) are found in the CNS in health and disease. Cellular sources are glial cells and neurons. Glial production of IL-6 has intensively been studied, but comparatively little is known about the induction of IL-6 in neurons. Emerging evidence suggests that IL-6 possesses neurotrophic properties. Recent data show that neuronal IL-6 expression is induced by excitatory amino acids or membrane depolarization. This implicates that IL-6 is produced not only under pathological conditions but may play a critical role as a physiological neuromodulator that is induced by neuronal activity and regulates brain functions. In the following article, the authors review the current data on IL-6 expression in neurons, with special reference to the induction of IL-6 by neuronal activity. They discuss its direct and indirect effects as a neuromodulator and speculate about the possible function of IL-6 as a physiological regulatory molecule and as a neuroprotective agent in brain pathology.

Down-regulation of IL-6 production by astaxanthin via ERK-, MSK-, and NF-κB-mediated signals in activated microglia

“…Increased levels of IL-6 in the brain have been linked to inflammation-related neuronal diseases and gliomas [8,9]. IL-6 expression in the brain increases after LPS injection and during the development of neurodegenerative disease [28].…”

“…An elevation of IL-6 levels is closely associated with many neurological disorders, including Alzheimer's disease, multiple sclerosis, and viral and bacterial infections [7]. Over-expression of IL-6 leads to neuropathology, including neurodegeneration, breakdown of the blood-brain barrier, angiogenesis, impaired learning, and influences glial cells as messengers between the immune system and the CNS [7][8][9].…”

Genes and outcome after aneurysmal subarachnoid haemorrhage

“…In these laboratory animals, the gene products of the expressed genes influence recovery after ischaemia [17,23,25,43]. In man, some of the corresponding genes have different variants (polymorphisms) leading to different protein isoforms or differences in level of protein expression.…”

Does an acute inflammatory response temporarily attenuate parasympathetic reactivation?

“…Inflammatory cytokines may affect autonomic balance by disturbing the hypothalamic-pituitary-adrenal axis at the level of the pituitary and adrenal glands [11].…”