Regulation of Body Temperature and Neuroprotection by Endogenous Interleukin-6 in Cerebral Ischemia

Herrmann, Oliver; Tarabin, Victoria; Suzuki, Shigeaki; Attigah, Nicolas; Coserea, Irinel; Schneider, Armin; Vogel, Johannes; Prinz, Simone; Schwab, Stefan; Monyer, Hannah; Brombacher, Frank; Schwaninger, Markus

doi:10.1097/01.wcb.0000055177.50448.fa

Cited by 99 publications

(28 citation statements)

References 64 publications

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“…On the other hand, the results that IL-6 upregulated CaN expression and activity in the presence of NMDA suggest that microenvironments around or/and within injured neurons, such as excessive Ca 2+ , may help to activate IL-6 signaling pathway. It has been shown that IL-6 level increases dramatically in many neurological disorders [12][13][14][15]. The increased IL-6 exerts compensatory neuroprotection against further neuronal injury or death [60].…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

Zhuang

Shen

et al. 2015

Cell Calcium

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Section: Discussionmentioning

confidence: 99%

“…IL-6 expression is low in the brain under normal conditions, but it increases dramatically in some neurological disorders, such as stroke, brain damage and seizures [12][13][14][15]. IL-6 role in the brain is complicated.…”

Section: Introductionmentioning

confidence: 98%

Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

Zhuang

Shen

et al. 2015

Cell Calcium

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“…In another report, GCA patients with ischemic events had lower IL-6 mRNA tissue expression and lower circulating IL-6 levels, while, compared to patients without ischemia, no significant differences were found for IL-1b and tumor necrosis factor 17 . IL-6 is known to be associated with fever 18,22 . In addition, angiogenesis in temporal artery sections was more prominent in patients with strong acute phase response, and in those without ischemic complications 6 .…”

Section: Systemic Manifestations and Inflammatory Responsementioning

confidence: 99%

Risk Factors for Cranial Ischemic Complications in Giant Cell Arteritis

Nesher

Berkun²,

Mates³

et al. 2004

Medicine

131

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Cranial ischemic complications (CICs) are among the presenting manifestations of giant cell arteritis (GCA). Yet patients with GCA may develop CICs at a later stage, despite steroid therapy. In the current report we delineate risk factors for CICs, both at presentation and during follow-up, and review the relevant literature. We reviewed charts of 175 patients with GCA. Follow-up data were available for 166 patients. CICs at presentation or developing within 2 weeks of GCA diagnosis were considered GCA related. CICs developing later were considered GCA related only when associated with other GCA-related manifestations or acute-phase reactions. Associations between CICs and other variables were tested by multivariate analysis. At presentation, 43 patients (24.6%) had CICs. Risk factors were transient cerebro-ophthalmic ischemic episodes (COIEs) (odds ratio [OR] 4.3) and male sex (OR 2.5), while the presence of systemic symptoms was "protective" (OR 0.3). During follow-up 8.4% of patients with GCA developed new CICs. Risk factors in these cases were previous CICs at presentation (OR 5.6) and transient COIEs developing during follow-up (OR 14.8). The use of low-dose aspirin was protective (OR 0.2). These data, together with data from the literature review, suggest that GCA patients with transient COIEs and without fever or other systemic symptoms are at increased risk of presenting with CICs. Risk factors for late-developing CICs were CICs at presentation and late-developing transient COIEs.

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“…IL-6 and its receptor (IL-6R) are expressed in neurons after ischemia (29)(30)(31), and it has been shown that i.c.v. injection of IL-6 in rats decreases the infarct volume (32), and endogenous IL-6 also plays a neuroprotective role through thermoregulation (33). More recently, IL-6R antibody injection increased infarct volume after ischemia (34).…”

mentioning

confidence: 99%

Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6

Ohtaki

Nakamachi

Dohi

et al. 2006

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

180

192

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Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to decrease ischemic neuronal damage and increase IL-6 secretion in rats. However, the mechanisms underlying neuroprotection are still to be fully elucidated. The present study was designed to investigate the role played by PACAP and IL-6 in mediating neuroprotection after ischemia in a null mouse. Infarct volume, neurological deficits, and cytochrome c in cytoplasm were higher in PACAP ؉/؊ and PACAP ؊/؊ mice than in PACAP ؉/؉ animals after focal ischemia, although the severity of response was ameliorated by the injection of PACAP38. A decrease in mitochondrial bcl-2 was also accentuated in PACAP ؉/؊ and PACAP ؊/؊ mice, but the decrease could be prevented by PACAP38 injection. PACAP receptor 1 (PAC1R) immunoreactivity was colocalized with IL-6 immunoreactivity in neurons, although the intensity of IL-6 immunoreactivity in PACAP ؉/؊ mice was less than that in PACAP ؉/؉ animals. IL-6 levels increased in response to PACAP38 injection, an effect that was canceled by cotreatment with the PAC1R antagonist. However, unlike in wild-type controls, PACAP38 treatment did not reduce the infarction in IL-6 null mice. To clarify the signaling pathway associated with the activity of PACAP and IL-6, phosphorylated STAT (signal transducer and activator of transcription) 3, ERK (extracellular signal-regulated kinase), and AKT levels were examined in PACAP ؉/؊ and IL-6 null mice after ischemia. Lower levels of pSTAT3 and pERK were observed in the PACAP ؉/؊ mice, whereas a reduction in pSTAT3 was recorded in the IL-6 null mice. These results suggest that PACAP prevents neuronal cell death after ischemia via a signaling mechanism involving IL-6.bcl-2 ͉ extracellular signal-regulated kinase ͉ ischemia ͉ pituitary adenylate cyclase-activating polypeptide-specific receptor ͉ signal transducer and activator of transcription 3

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Regulation of Body Temperature and Neuroprotection by Endogenous Interleukin-6 in Cerebral Ischemia

Cited by 99 publications

References 64 publications

Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

Risk Factors for Cranial Ischemic Complications in Giant Cell Arteritis

Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6

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