Interleukin-6 as a neurotrophic factor for promoting the survival of cultured basal forebrain cholinergic neurons from postnatal rats

Hama, Tokiko; Miyamoto, Masabumi; Tsukui, Hiroko; Nishio, Chika; Hatanaka, Hiroshi

doi:10.1016/0304-3940(89)90600-9

Cited by 242 publications

(86 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NGF biosynthesis in the injured brain can be induced by IL-6 through its effects on neurons, microglia and astrocytes, as similar neuroprotective mechanisms have been recognized both in traumatic and ischemic lesions. [35][36][37] Furthermore, IL-6 up-regulation has been found using cerebral micro dialysis probes in head-injured adult patients 34 and our results are consistent with this study, confirming that IL-6 is an endogenous neuroprotective cytokine produced in response to brain injury. Also neurotrophic factors have been shown to play a neuroprotective role in different CNS dysfunctions.…”

Section: Discussionsupporting

confidence: 81%

Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children

Chiaretti

Antonelli

Riccardi

et al. 2008

European Journal of Paediatric Neurology

View full text Add to dashboard Cite

Background-Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. In particular, interleukin 1β (IL-1β) is associated with neuronal damage, while interleukin 6 (IL-6) exerts a neuroprotective role due to its ability to modulate neurotrophins biosynthesis. However, the relationship between these cytokines and neurotrophins with the severity and outcome of TBI remains still controversial.Aims-To determine whether the concentration of IL-1β and IL-6 and neurotrophins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and its neurologic outcome.Methods-Prospective observational clinical study in a university hospital. CSF samples were collected from 27 children at 2h (Time T1) and 48h (Time T2) after severe TBI, and from 21 matched controls. Severity of TBI was evaluated by GCS and neurologic outcome by GOS. CSF concentrations of cytokines and neurotrophins were measured by immunoenzymatic assays.Results-Early NGF and IL-1β concentrations (T1) correlated significantly with the severity of head injury, whereas no correlation was found for IL-6, BDNF, and GDNF. Furthermore, higher NGF and IL-6 and lower IL-1β expression at T2 were associated with better neurologic outcomes. No significant association was found between BDNF or GDNF expression and neurologic outcome.Conclusions-NGF concentration in CSF is a useful marker of brain damage following severe TBI and its up-regulation, in the first 48 h after head injury together with lower IL-1β expression, correlates with a favorable neurologic outcome. Clinical and prognostic information may also be obtained from IL-6 expression.

show abstract

Section: Discussionsupporting

confidence: 81%

Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children

Chiaretti

Antonelli

Riccardi

et al. 2008

European Journal of Paediatric Neurology

View full text Add to dashboard Cite

show abstract

“…It is unlikely that neuronal injury or death observed in GFAP-IL6 mice is due to direct toxicity mediated by IL-6. First, addition of different concentrations of IL-6 to cultured hippocampal neurons was reported to be associated with a trophic rather than a neurotoxic effect of the cytokine (17,18). Second, in heterozygous GFAP-IL6 mice expression of transgene-encoded IL-6 was shown previously to be maximal by 3 months of age (8).…”

Section: Resultsmentioning

confidence: 99%

Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain

Heyser

Masliah

Samimi

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

349

206

View full text Add to dashboard Cite

Inf lammation with expression of interleukin 6 (IL-6) in the brain occurs in many neurodegenerative disorders. To better understand the role of IL-6 in such disorders, we examined performance in a learning task in conjunction with molecular and cellular neuropathology in transgenic mice that express IL-6 chronically from astrocytes in the brain. Transgenic mice exhibited dose-and age-related deficits in avoidance learning that closely corresponded with specific progressive neuropathological changes. These results establish a link between the central nervous system expression of IL-6, inf lammatory neurodegeneration, and a learning impairment in transgenic mice. They suggest a critical role for a proinf lammatory cytokine in the cognitive deficits and associated neuroinf lammatory changes that have been documented in neurodegenerative diseases such as Alzheimer disease and AIDS.

show abstract

“…IL-6 has been shown to have beneficial potential in the CNS because of its neurotrophic and neuroprotective effects (Satoh et al, 1988;Hama et al, 1989;Gadient and Otten, 1997;Loddick et al, 1998;März et al, 1998b), and anti-inflammatory actions through the inhibition of VCAM-1, intercellular adhesion molecule-1, and TNF-␣ expression by CNS cells Shrikant et al, 1995;Oh et al, 1998). However, other reports suggest that IL-6 is detrimental and adds to the pathophysiology associated with CNS disorders (Campbell et al, 1993;Klein et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

et al. 1999

View full text Add to dashboard Cite

In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-α or IL-1β on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-α or IL-1β plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-α- or IL-1β-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-α or IL-1β plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-α for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-α and IL-1β.

show abstract

Interleukin-6 as a neurotrophic factor for promoting the survival of cultured basal forebrain cholinergic neurons from postnatal rats

Cited by 242 publications

References 17 publications

Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children

Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children

Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

Contact Info

Product

Resources

About