Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2016 | Short report

Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage

Authors: Aichi Niwa, Koji Osuka, Takahiro Nakura, Naoki Matsuo, Takeya Watabe, Masakazu Takayasu

Published in: Journal of Neuroinflammation | Issue 1/2016

Abstract

Background

Interleukin-6 (IL-6), an inflammatory cytokine, plays important roles in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Chemokines are chemoattractant cytokines that regulate trafficking of monocytes/macrophages and lymphocytes to sites of inflammation. However, no studies have been reported regarding the temporal expression of these cytokines in CSF after SAH.

Findings

The concentrations of IL-6, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) in the CSF of ten patients with SAH were measured using ELISA kits over a period of 14 days. All aneurysms were located in the anterior circulation. CSF samples from patients with unruptured aneurysms were used as controls. The concentration of IL-6 significantly increased during the acute stage of the disease. The concentration of MCP-1 increased from days 1 to 5, peaking on day 3, and decreased thereafter. The concentrations of IP-10 and MIG progressively increased, peaked on day 5, and then gradually decreased. There were strong correlations between the maximum levels of IL-6 and MCP-1 and IP-10 and MIG on day 5. The maximum level of IL-6 was much higher in poor outcome patients than in good outcome patients.

Conclusions

The present investigation demonstrated that increases in IL-6 levels may induce the expression of MCP-1 in CSF after SAH, followed by increases in the expression of IP-10 and MIG. Dynamic changes in the levels of these cytokines may induce inflammation and may be closely associated with the development of delayed ischemic neurological deficits after SAH.

Available only for authorised users

Nagata K, Sasaki T, Mori T, Nikaido H, Kobayashi E, Kim P, Kirino T. Cisternal talc injection in dog can induce delayed and prolonged arterial constriction resembling cerebral vasospasm morphologically and pharmacologically. Surg Neurol. 1996;45:442–7.CrossRefPubMed

Peterson JW, Kwun BD, Hackett JD, Zervas NT. The role of inflammation in experimental cerebral vasospasm. J Neurosurg. 1990;72:767–74.CrossRefPubMed

Chaichana KL, Pradilla G, Huang J, Tamargo RJ. Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage. World Neurosurg. 2010;73:22–41.CrossRefPubMed

Mathiesen T, Andersson B, Loftenius A, von Holst H. Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg. 1993;78:562–7.CrossRefPubMed

Fassbender K, Ries S, Schminke U, Schneider S, Hennerici M. Inflammatory cytokines in CSF in bacterial meningitis: association with altered blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry. 1996;61:57–61.CrossRefPubMedPubMedCentral

Kuhle J, Lindberg RL, Regeniter A, Mehling M, Steck AJ, Kappos L, Czaplinski A. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol. 2009;16:771–4.CrossRefPubMed

Mahad DJ, Howell SJ, Woodroofe MN. Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002;72:498–502.PubMedPubMedCentral

Kim GH, Kellner CP, Hahn DK, Desantis BM, Musabbir M, Starke RM, Rynkowski M, Komotar RJ, Otten ML, Sciacca R, et al. Monocyte chemoattractant protein-1 predicts outcome and vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2008;109:38–43.CrossRefPubMed

Osuka K, Suzuki Y, Tanazawa T, Hattori K, Yamamoto N, Takayasu M, Shibuya M, Yoshida J. Interleukin-6 and development of vasospasm after subarachnoid haemorrhage. Acta Neurochir (Wien). 1998;140:943–51.CrossRef

10.

Osuka K, Watanabe Y, Yamauchi K, Nakazawa A, Usuda N, Tokuda M, Yoshida J. Activation of the JAK-STAT signaling pathway in the rat basilar artery after subarachnoid hemorrhage. Brain Res. 2006;1072:1–7.CrossRefPubMed

11.

Schoch B, Regel JP, Wichert M, Gasser T, Volbracht L, Stolke D. Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery. 2007;60:828–36. discussion 828-836.CrossRefPubMed

12.

Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6:315–25.CrossRefPubMed

13.

Kubota T, Handa Y, Tsuchida A, Kaneko M, Kobayashi H, Kubota T. The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke. 1993;24:1993–2000. discussion 2000-2001.CrossRefPubMed

14.

Lu H, Shi JX, Chen HL, Hang CH, Wang HD, Yin HX. Expression of monocyte chemoattractant protein-1 in the cerebral artery after experimental subarachnoid hemorrhage. Brain Res. 2009;1262:73–80.CrossRefPubMed

15.

Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Tuohy VK. Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB J. 1993;7:592–600.PubMed

16.

Lahrtz F, Piali L, Nadal D, Pfister HW, Spanaus KS, Baggiolini M, Fontana A. Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon-g inducible protein-10 and monocyte chemotactic protein-1. Eur J Immunol. 1997;27:2484–9.CrossRefPubMed

17.

Ruschpler P, Lorenz P, Eichler W, Koczan D, Hanel C, Scholz R, Melzer C, Thiesen HJ, Stiehl P. High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis. Arthritis Res Ther. 2003;5:R241–252.CrossRefPubMedPubMedCentral

18.

Carter SL, Muller M, Manders PM, Campbell IL. Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro. Glia. 2007;55:1728–39.CrossRefPubMed

19.

Engelhardt E, Toksoy A, Goebeler M, Debus S, Brocker EB, Gillitzer R. Chemokines IL-8, GROa, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am J Pathol. 1998;153:1849–60.CrossRefPubMedPubMedCentral

Title: Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage
Authors: Aichi Niwa
Koji Osuka
Takahiro Nakura
Naoki Matsuo
Takeya Watabe
Masakazu Takayasu
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-016-0675-7

At a glance: The STEP trials

Springer Medicine

Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage

Abstract

Background

Findings

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Brain trauma elicits non-canonical macrophage activation states

Intra-amniotic LPS causes acute neuroinflammation in preterm rhesus macaques

A monoclonal natural human IgM protects axons in the absence of remyelination

The extracellular matrix protein laminin-10 promotes blood–brain barrier repair after hypoxia and inflammation in vitro

Cuprizone demyelination induces a unique inflammatory response in the subventricular zone

Celastrol protects mouse retinas from bright light-induced degeneration through inhibition of oxidative stress and inflammation