Background and Purpose: Rebleeding in spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality among stroke survivors. Due to the links between inflammation and rebleeding, we hypothesized that the biomarkers of inflammation are associated with the pathogenesis of rebleeding in ICH. We sought to investigate whether these biomarkers and clinical variables on admission can provide prognostic information on the risk of rebleeding. Methods: This prospective study enrolled 59 consecutive patients with spontaneous ICH. We determined the concentrations of interleukin-10 (IL-10), intercellular adhesion molecule-1, and complement 3 in blood samples obtained on admission. Results: Univariate analysis indicated that hematoma volume, leukocyte count, hydrocephalus, and plasma IL-10 levels were associated with rebleeding. Multivariate logistic regression analysis indicated that hydrocephalus (95% CI of OR, 1.6–26.7) and IL-10 (95% CI of OR, 1.03–1.22) were independently associated with an increased probability of rebleeding. Conclusion: These data suggest that IL-10, a molecular biomarker of inflammatory response in the early acute phase of ICH, is associated with subsequent rebleeding.

Keywords:
Rebleeding, Intracerebral hemorrhage, spontaneous, Interleukin-10
1.
Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T: Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke 1996;27:1783–1787.
2.
Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, Spilker J, Duldner J, Khouri J: Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1–5.
3.
Fujii Y, Tanaka R, Takeuchi S, Koike T, Minakawa T, Sasaki O: Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 1994;80:51–57.
4.
Lee KR, Kawai N, Seoung K, Sagher O, Hoff J: Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood brain barrier permeability and cell survival in a rat model. J Neurosurg 1997;86:272–278.
5.
Xi G, Wagner KR, Keep RF, Hua Y, de Courten-Mayers G, Broderick JP, Brott TG, Hoff JT: Role of blood clot formation on early edema development after experimental intracerebral hemorrhage. Stroke 1998;29:2580–2586.
6.
Rosenberg GA, Navratil M: Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat. Neurology 1997;48:921–926.
7.
Wang J, Doré S: Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007;27:894–908.
8.
Jennett B, Bond M: Assessment of outcome after severe brain damage. Lancet 1975;i:480–484.
9.
Greenberg MS: Handbook of Neurosurgery, ed 7. Stuttgart, Thieme, 2006, pp 307–313.
10.
Jawa RS, Kulaylat MN, Baumann H, Dayton MT: What is new in cytokine research related to trauma/critical care. J Intensive Care Med 2006;21:63–85.
11.
van der Poll T, van Deventer S: Cytokines and anticytokines in the pathogenesis of sepsis. Infect Dis Clin North Am 1999;13:413–426, ix.
12.
Lee KR, Kawai N, Seoung K, Sagher O, Hoff JT: Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood brain barrier permeability and cell survival in a rat model. J Neurosurg 1997;86:272–278.
13.
Hamman GF, Okada Y, Fitridge R, Del Zoppo GJ: Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion. Stroke 1995;26:2120–2126.
14.
Horstmann S, Kalb P, Koziol J, Gardner H, Wagner S: Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients. Influence of different therapies. Stroke 2003;34:2165–2172.
15.
Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schining B, Glockner F, Lanksch WR, Volk HD, Docke WD: Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 1998;4:808–813.
16.
Mocco J, Mack WJ, Ducruet AF, Sosunov SA, Sughrue ME, Hassid BG, Nair MN, Laufer I, Komotar RJ, Claire M, Holland H, Pinsky DJ, Connolly ES Jr: Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 2006;99:209–217.
17.
Peerschke EI, Reid KB, Ghebrehiwet B: Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity. J Exp Med 1993;178:579–587.
18.
Murphy HS, Shayman JA, Till GO, Mahrougui M, Owens CB, Ryan US, Ward PA: Superoxide responses of endothelial cells to C5a and TNFalpha: divergent signal transduction pathways. Am J Physiol 1992;263:L51–L59.
19.
Hanley DF: Intraventricular hemorrhage: severity factor and treatment target in spontaneous intracerebral hemorrhage.Stroke 2009;40:1533–1538.
20.
Fogelholm R, Murros K, Rissanen A, Avikainen S: Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study. J Neurol Neurosurg Psychiatry 2005;76:349–353.
21.
Valade N, Decailliot F, Rébufat Y, Heurtematte Y, Duvaldestin P, Stéphan F: Thrombocytosis after trauma: incidence, aetiology, and clinical significance. Br J Anaesth 2005;94:18–23.
22.
Desborough JP: The stress response to trauma and surgery. Br J Anaesth 2000;85:109–117.
23.
Wallace LK, Starr NJ, Leventhal MJ, Estafanous FG: Hyperglycemia on ICU admission after CABG is associated with increased risk of mediastinitis or wound infection. Anesthesiology 1996;85(suppl):A286.
24.
Asadullah K, Sterry W, Volk HD: Interleukin-10 therapy – review of a new approach. Pharmacol Rev 2003;55:241–269.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.