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J Neurol Surg A Cent Eur Neurosurg 2018; 79(02): 145-151
DOI: 10.1055/s-0037-1604084
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage

Kamil Ďuriš
1   Department of Neurosurgery, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
2   Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Eduard Neuman
1   Department of Neurosurgery, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Václav Vybíhal
1   Department of Neurosurgery, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Vilém Juráň
1   Department of Neurosurgery, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Jana Gottwaldová
3   Department of Clinical Biochemistry, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Michal Kýr
4   Department of Pediatric Oncology, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Anna Vašků
2   Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Martin Smrčka
1   Department of Neurosurgery, The University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
› Author Affiliations
Further Information

Publication History

23 September 2016

16 February 2017

Publication Date:
04 September 2017 (online)

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Abstract

Background Subarachnoid hemorrhage (SAH) is a severe condition associated with high mortality. Early brain injury (EBI) plays an important role in the pathophysiology of SAH, and inflammation is a major contributor to EBI. Inflammation is a widely studied topic in both experimental and clinical conditions; however, just a few clinical studies have focused primarily on the early inflammatory response after SAH, and detailed information about the association between the dynamics of early inflammatory response with main clinical characteristics is lacking. This study analyzes the early dynamics of inflammatory response after SAH and evaluates the possible associations between the markers of early inflammatory response and main clinical characteristics.

Patients and Methods A total of 47 patients with a diagnosis of aneurysmal SAH within the last 24 hours were enrolled in the study. All treatments, including treatment of aneurysm (surgery/coiling) and implantation of a drainage system (external ventricular drainage/lumbar catheter), were conducted in the same way as in other patients with this diagnosis. Blood and cerebrospinal fluid (CSF) samples were collected three times a day for 4 days. The dynamics of proinflammatory cytokines were assessed, and associations between levels of the proinflammatory cytokines interleukin (IL)-6, IL-1β, or tumor necrosis factor (TNF)α and main clinical characteristics were evaluated using linear mixed-effect models.

Results The CSF levels of IL-6 were massively increased initially after SAH (up to 72 hours) with an additional increase in later phases (after 72 hours), but there was high variability in IL-6 levels. A significant association was noted between the Glasgow Outcome Scale score and both overall levels of IL-6 (p = 0.0095) and their dynamics (p = 0.0208); the effect of the Hunt and Hess scale was borderline (p = 0.0887). No association was found between IL-6 levels and Fisher grade, modality of treatment (surgery, coiling, no treatment), and later development of cerebral vasospasm. Plasmatic levels of IL-6 increased slightly, but no significant association was found. The levels of IL-1β and TNFα were within the physiologic range in both CSF and plasma.

Conclusions Early dynamics of IL-6 in CSF are associated with a patient́s outcome. But it is difficult to use IL-6 alone for outcome prediction due to its high variability. The question is whether the dynamics of IL-6 could be used in combination with other early markers associated with brain injury. More detailed research is required to answer this question.

Keywords

subarachnoid hemorrhage - early brain injury - inflammation - IL-6
 

  • References

  • 1 Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 2010; 41 (08) e519-e536
    CrossrefPubMedGoogle Scholar
  • 2 Kienzler J, Marbacher S, Remonda L. , et al. Outcome after in-hospital rebleeding of rupture of intracranial aneurysms. J Neurol Surg A Cent Eur Neurosurg 2016; 77 (03) 207-221
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid haemorrhage. Lancet 2007; 369 (9558): 306-318
    CrossrefPubMedGoogle Scholar
  • 4 Jurák L, Buchvald P, Beneš V, Kaiser M, Suchomel P. Vasospasms as a complication of subarachnoid hemorrhage—a case report. Ces Slov Neurol Neurochir 2014; 77/110 (05) 642-646
    PubMedGoogle Scholar
  • 5 Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJH, Rinkel GJE. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 2009; 51 (12) 813-819
    CrossrefPubMedGoogle Scholar
  • 6 Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KTS. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth 2012; 109 (03) 315-329
    CrossrefPubMedGoogle Scholar
  • 7 Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 2013; 4 (04) 432-446
    CrossrefPubMedGoogle Scholar
  • 8 Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 2006; 28 (04) 399-414
    CrossrefPubMedGoogle Scholar
  • 9 Nishizawa S. The roles of early brain injury in cerebral vasospasm following subarachnoid hemorrhage: from clinical and scientific aspects. Acta Neurochir Suppl (Wien) 2013; 115: 207-211
    PubMedGoogle Scholar
  • 10 Cahill J, Calvert JH, Zhang JH. Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 2006; 26 (11) 1341-1353
    CrossrefPubMedGoogle Scholar
  • 11 Aihara Y, Kasuya H, Onda H, Hori T, Takeda J. Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke 2001; 32 (01) 212-217
    CrossrefPubMedGoogle Scholar
  • 12 Kaestner S, Dimitriou I. TGF beta1 and TGF beta2 and their role in posthemorrhagic hydrocephalus following SAH and IVH. J Neurol Surg A Cent Eur Neurosurg 2013; 74 (05) 279-284
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Wu W, Guan Y, Zhao G. , et al. Elevated IL-6 and TNF-α levels in cerebrospinal fluid of subarachnoid hemorrhage patients. Mol Neurobiol 2016; 53 (05) 3277-3285
    CrossrefPubMedGoogle Scholar
  • 14 Ni W, Gu YX, Song DL, Leng B, Li PL, Mao Y. The relationship between IL-6 in CSF and occurrence of vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl (Wien) 2011; 110 (Pt 1): 203-208
    PubMedGoogle Scholar
  • 15 Sarrafzadeh A, Schlenk F, Gericke C, Vajkoczy P. Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage. Neurocrit Care 2010; 13 (03) 339-346
    CrossrefPubMedGoogle Scholar
  • 16 Hopkins SJ, McMahon CJ, Singh N. , et al. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J Neuroinflammation 2012; 9: 255
    PubMedGoogle Scholar
  • 17 Höllig A, Remmel D, Stoffel-Wagner B, Schubert GA, Coburn M, Clusmann H. Association of early inflammatory parameters after subarachnoid hemorrhage with functional outcome: a prospective cohort study. Clin Neurol Neurosurg 2015; 138: 177-183
    CrossrefPubMedGoogle Scholar
  • 18 Muroi C, Hugelshofer M, Seule M. , et al. Correlation among systemic inflammatory parameter, occurrence of delayed neurological deficits, and outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 2013; 72 (03) 367-375 ; discussion 375
    CrossrefPubMedGoogle Scholar
  • 19 Connolly Jr ES, Rabinstein AA, Carhuapoma JR. , et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012; 43 (06) 1711-1737
    CrossrefPubMedGoogle Scholar
  • 20 Shimamura N, Naraoka M, Katagai T. , et al. Analysis of factors that influence long-term independent living for elderly subarachnoid hemorrhage patients. World Neurosurg 2016; 90: 504-510
    CrossrefPubMedGoogle Scholar
  • 21 Frijns CJM, Rinkel GJE, Castigliego D, Van Gijn J, Sixma JJ, Fijnheer R. Endothelial cell activation after subarachnoid hemorrhage. Neurosurgery 2002; 50 (06) 1223-1229 ; discussion 1229–1230
    PubMedGoogle Scholar
  • 22 Ma CX, Yin WN, Cai BW. , et al. Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage. Chin Med J (Engl) 2009; 122 (13) 1575-1581
    PubMedGoogle Scholar
  • 23 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 (12) 1993-2000 ; discussion 2000–2001
    CrossrefPubMedGoogle Scholar
  • 24 Hirashima Y, Nakamura S, Endo S, Kuwayama N, Naruse Y, Takaku A. Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage. Neurochem Res 1997; 22 (10) 1249-1255
    CrossrefPubMedGoogle Scholar
  • 25 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. Neuroendocrinol Lett 2004; 25 (1–2): 141-147
    PubMedGoogle Scholar
  • 26 Mathiesen T, Andersson B, Loftenius A, von Holst H. Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 1993; 78 (04) 562-567
    CrossrefPubMedGoogle Scholar
  • 27 Osuka K, Suzuki Y, Tanazawa T. , et al. Interleukin-6 and development of vasospasm after subarachnoid haemorrhage. Acta Neurochir (Wien) 1998; 140 (09) 943-951
    CrossrefPubMedGoogle Scholar
  • 28 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 (05) 828-836 ; discussion 828–836
    CrossrefPubMedGoogle Scholar
  • 29 Rex S, Kraemer S, Grieb G. , et al. The role of macrophage migration inhibitory factor in critical illness. Mini Rev Med Chem 2014; 14 (14) 1116-1124
    PubMedGoogle Scholar