Skip to main content

Advertisement

SpringerLink
Log in

High-Mobility Group Box 1 Protein in CSF of Patients with Subarachnoid Hemorrhage

  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

High-mobility group box 1 protein (HMGB1) is a nuclear factor that is a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. The inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH) have been reported previously, but HMGB1 has not. In this study, we measured HMGB1 and the inflammatory cytokines in the CSF of patients with SAH.

Methods

CSF samples were collected on days 3, 7, and 14 from the drainage tubes of the postaneurysm clips of 39 patients with SAH. HMGB1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α) were measured in the CSF, and compared between the patients with favorable (good recovery and moderate disability) and unfavorable outcomes (severe disability, vegetative state, and death) at 3 months.

Results

In the unfavorable outcome group, HMGB1 (P = 0.017), IL-6 (P = 0.003), IL-8 (P = 0.041), and TNF-α (P = 0.002) were significantly increased. HMGB1 correlated significantly with IL-6, IL-8, and TNF-α (R = 0.672, 0.421, and 0.697, respectively).

Conclusions

HMGB1 was increased in the CSF of SAH patients with an unfavorable outcome, as were the other cytokines. These results suggest that HMGB1 and cytokines are related to the brain damage observed after SAH. HMGB1 might play a key role in the inflammatory response in the CNS of SAH patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Anderson UG, Tracey KJ. HMGB1, a pro-inflammatory cytokine of clinical interest. J Intern Med. 2004;255:318–9.

    Article  Google Scholar 

  2. Yan H, Wang H, Czura CJ, Tracey KJ. The cytokine activity of HMGB1. J Leukoc Biol. 2005;78:1–8.

    Article  Google Scholar 

  3. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–51.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Kikuchi T, Okuda Y, Kaito N, et al. Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage. Neurol Res. 1995;17:106–8.

    CAS  PubMed  Google Scholar 

  6. Gaetani P, Tartara F, Pignatti P, et al. Cisternal CSF levels of cytokines after subarachnoid hemorrhage. Neurol Res. 1998;20:337–42.

    CAS  PubMed  Google Scholar 

  7. Osuka K, Suzuki Y, Tanazawa T, et al. Interleukin-6 and development of vasospasm after subarachnoid haemorrhage. Acta Neurochir. 1998;140:943–51.

    Article  CAS  Google Scholar 

  8. Hendryk S, Jarzab B, Josko J. Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuro Endocrinol Lett. 2004;25:141–7.

    CAS  PubMed  Google Scholar 

  9. Takizawa T, Tada T, Kitazawa K, et al. Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res. 2001;23:724–30.

    Article  CAS  PubMed  Google Scholar 

  10. Oda Y, Tsuruta R, Kasaoka S, Inoue T, Maekawa T. The cutoff values of intrathecal interleukin 8 and 6 for predicting the neurological outcome in cardiac arrest victims. Resuscitation. 2009;80:189–93.

    Article  CAS  PubMed  Google Scholar 

  11. Wang H, Vishnubhakat JM, Bloom O, et al. Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes. Surgery. 1999;126:389–92.

    CAS  PubMed  Google Scholar 

  12. Pullerits R, Jonsson IM, Kollias G, Tarkowski A. Induction of arthritis by high mobility group box chromosomal protein 1 is independent of tumour necrosis factor signaling. Arthritis Res Ther. 2008;10:R72.

    Article  PubMed  Google Scholar 

  13. Baumann H, Gauldie J. Acute phase response. Immunol Today. 1994;15:74–80.

    Article  CAS  PubMed  Google Scholar 

  14. Lennihan L, Mayer SA, Fink ME, et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage, a randomized control trial. Stroke. 2000;31:383–91.

    CAS  PubMed  Google Scholar 

  15. Yamada S, Inoue K, Yakabe K, Imaizumi H, Maruyama I. High mobility group protein 1 (HMGB1) quantified by ELISA with a monoclonal antibody that does not cross-react with HMGB2. Clin Chem. 2003;49:1535–7.

    Article  CAS  PubMed  Google Scholar 

  16. Morgan E, Varro R, Sepulveda H, et al. Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin Immunol. 2004;110:252–66.

    Article  CAS  PubMed  Google Scholar 

  17. Agnello D, Wang H, Yang H, Tracey KL, Ghezzi P. HMGB1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion. Cytokine. 2002;18:231–6.

    Article  CAS  PubMed  Google Scholar 

  18. Harris HE, Anderson U. The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004;34:1503–12.

    Article  Google Scholar 

  19. Takata K, Kitamura Y, Tsuchiya D, Kawasaki T, Taniguchi T, Shimohama S. High mobility group box protein-1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity. J Neurosci Res. 2004;78:880–91.

    Article  CAS  PubMed  Google Scholar 

  20. Andersson BU, Wang H, Palmblad K, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192:565–70.

    Article  CAS  PubMed  Google Scholar 

  21. Randon-Mitchell BR, Ochiai M, Li J, et al. IFN-γ induces high mobility group box 1 protein release partly through a TNF-dependent mechanism. J Immunology. 2003;170:3890–7.

    Google Scholar 

  22. Kim JB, Choi JS, Yu YM, et al. HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci. 2006;26:6413–21.

    Article  CAS  PubMed  Google Scholar 

  23. Mathiesen T, Edner G, Ulfarsson E, Andersson B. Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-α following subarachnoid hemorrhage. J Neurosurg. 1997;87:215–20.

    Article  CAS  PubMed  Google Scholar 

  24. Faraco G, Fossati S, Bianchi ME, et al. High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo. J Neurochem. 2007;31:1–13.

    Google Scholar 

  25. Kimura H, Gules I, Meguro T, Zhang JH. Cytotoxicity of cytokines in cerebral microvascular endotherial cell. Brain Res. 2003;990:148–56.

    Article  CAS  PubMed  Google Scholar 

  26. Gong Q, Xu JF, Yin H, Liu SF, Duan LH, Bian ZL. Protective effect of antagonist of high-mobility group box 1 on lipopolysaccharide-induced acute lung injury in mice. Scand J Immunol. 2009;69:29–35.

    Article  CAS  PubMed  Google Scholar 

  27. Tang D, Kang R, Xiao W, et al. Quercetin prevents lipopolysaccharide-induced HMGB1 release and proinflammatory function. Am J Respir Cell Mol Biol 2009 (in press).

Download references

Acknowledgments

This clinical study was supported by a research project grant from the Japanese Ministry of Health, Labor, and Welfare (No. H18-trans-general-003). We are grateful to Kiyoshi Ichihara and Yuji Koyanagi (Department of Laboratory Science, Yamaguchi University Graduate School of Medicine) for their valuable statistical assistance, Taku Miyasho (Rakuno Gakuen University) and Hitomi Ikemoto (Yamaguchi University) for their valuable technical assistance with the measurements. We also thank Masako Ueda for assistance with the grant-related paperwork.

Conflict of interest statement

All work was conducted independently of the funding parties, except for a governmental grant. This grant had no influence on the decisions relating to the study design or publication.

Author information

Authors and Affiliations

  1. Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube, Yamaguchi, Japan

    Takashi Nakahara, Ryosuke Tsuruta, Tadashi Kaneko, Susumu Yamashita, Motoki Fujita, Shunji Kasaoka & Tsuyoshi Maekawa

  2. Department of Laboratory Medicine, Kagoshima University Hospital, Kagoshima, Japan

    Teruto Hashiguchi & Ikuro Maruyama

  3. Department of Neurosurgery, Yamaguchi University Hospital, Ube, Yamaguchi, Japan

    Michiyasu Suzuki

Authors
  1. Takashi Nakahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryosuke Tsuruta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tadashi Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susumu Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Motoki Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shunji Kasaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Teruto Hashiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michiyasu Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ikuro Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tsuyoshi Maekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tadashi Kaneko.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakahara, T., Tsuruta, R., Kaneko, T. et al. High-Mobility Group Box 1 Protein in CSF of Patients with Subarachnoid Hemorrhage. Neurocrit Care 11, 362–368 (2009). https://doi.org/10.1007/s12028-009-9276-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-009-9276-y

Keywords

Search

Navigation