Skip to main content
Erschienen in: Neurocritical Care 1/2014

01.08.2014 | Original Article

Stroke, IL-1ra, IL1RN, Infection and Outcome

verfasst von: Kyra J. Becker, Dorender Dankwa, Richard Lee, Juliane Schulze, Dannielle Zierath, Patricia Tanzi, Kevin Cain, Alexander Dressel, Dean Shibata, Jonathan Weinstein

Erschienen in: Neurocritical Care | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome.

Methods

Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism.

Results

In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome.

Conclusions

These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke.
Literatur
2.
Zurück zum Zitat Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB. The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci. Genomics. 1992;13:654–7.PubMedCrossRef Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB. The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci. Genomics. 1992;13:654–7.PubMedCrossRef
3.
Zurück zum Zitat Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38.PubMedCrossRef Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38.PubMedCrossRef
4.
Zurück zum Zitat Banwell V, Sena ES, Macleod MR. Systematic review and stratified meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke. J Stroke Cerebrovasc Dis. 2009;18:269–76.PubMedCrossRef Banwell V, Sena ES, Macleod MR. Systematic review and stratified meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke. J Stroke Cerebrovasc Dis. 2009;18:269–76.PubMedCrossRef
5.
Zurück zum Zitat Tanzi P, Cain K, Kalil A, et al. Post-stroke infection: a role for IL-1ra? Neurocrit Care. 2011;14:244–52.PubMedCrossRef Tanzi P, Cain K, Kalil A, et al. Post-stroke infection: a role for IL-1ra? Neurocrit Care. 2011;14:244–52.PubMedCrossRef
6.
Zurück zum Zitat Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011;11:110.PubMedCentralPubMedCrossRef Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011;11:110.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Aslanyan S, Weir CJ, Diener HC, Kaste M, Lees KR. Pneumonia and urinary tract infection after acute ischemic stroke: a tertiary analysis of the GAIN International trial. Eur J Neurol. 2004;11:49–53.PubMedCrossRef Aslanyan S, Weir CJ, Diener HC, Kaste M, Lees KR. Pneumonia and urinary tract infection after acute ischemic stroke: a tertiary analysis of the GAIN International trial. Eur J Neurol. 2004;11:49–53.PubMedCrossRef
8.
Zurück zum Zitat Danis VA, Millington M, Hyland VJ, Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol. 1995;99:303–10.PubMedCentralPubMedCrossRef Danis VA, Millington M, Hyland VJ, Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol. 1995;99:303–10.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Hurme M, Santtila S. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;28:2598–602.PubMedCrossRef Hurme M, Santtila S. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;28:2598–602.PubMedCrossRef
10.
Zurück zum Zitat Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol. 1998;47:195–8.PubMedCrossRef Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol. 1998;47:195–8.PubMedCrossRef
11.
Zurück zum Zitat Candiotti KA, Yang Z, Morris R, et al. Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption. Anesthesiology. 2011;114:1162–8.PubMedCrossRef Candiotti KA, Yang Z, Morris R, et al. Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption. Anesthesiology. 2011;114:1162–8.PubMedCrossRef
12.
Zurück zum Zitat Tountas NA, Casini-Raggi V, Yang H, et al. Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis. Gastroenterology. 1999;117:806–13.PubMedCrossRef Tountas NA, Casini-Raggi V, Yang H, et al. Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis. Gastroenterology. 1999;117:806–13.PubMedCrossRef
13.
Zurück zum Zitat Rocha AM, De Souza C, Rocha GA, et al. IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia. Br J Haematol. 2010;150:679–84.PubMedCrossRef Rocha AM, De Souza C, Rocha GA, et al. IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia. Br J Haematol. 2010;150:679–84.PubMedCrossRef
14.
Zurück zum Zitat Smolonska J, Wijmenga C, Postma DS, Boezen HM. Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research. Am J Respir Crit Care Med. 2009;180:618–31.PubMedCrossRef Smolonska J, Wijmenga C, Postma DS, Boezen HM. Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research. Am J Respir Crit Care Med. 2009;180:618–31.PubMedCrossRef
15.
Zurück zum Zitat Queiroz DM, Oliveira AG, Saraiva IE, et al. Immune response and gene polymorphism profiles in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2009;15:353–8.PubMedCrossRef Queiroz DM, Oliveira AG, Saraiva IE, et al. Immune response and gene polymorphism profiles in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2009;15:353–8.PubMedCrossRef
16.
Zurück zum Zitat Vencovsky J, Jarosova K, Ruzickova S, et al. Higher frequency of allele 2 of the interleukin-1 receptor antagonist gene in patients with juvenile idiopathic arthritis. Arthritis Rheum. 2001;44:2387–91.PubMedCrossRef Vencovsky J, Jarosova K, Ruzickova S, et al. Higher frequency of allele 2 of the interleukin-1 receptor antagonist gene in patients with juvenile idiopathic arthritis. Arthritis Rheum. 2001;44:2387–91.PubMedCrossRef
17.
Zurück zum Zitat Xue H, Lin B, Ni P, Xu H, Huang G. Interleukin-1B and interleukin-1 RN polymorphisms and gastric carcinoma risk: a meta-analysis. J Gastroenterol Hepatol. 2010;25:1604–17.PubMedCrossRef Xue H, Lin B, Ni P, Xu H, Huang G. Interleukin-1B and interleukin-1 RN polymorphisms and gastric carcinoma risk: a meta-analysis. J Gastroenterol Hepatol. 2010;25:1604–17.PubMedCrossRef
18.
Zurück zum Zitat Gromadzka G, Sarzynska-Dlugosz I, Czlonkowska A. IL1RN intron 2 polymorphism caused by variable number tandem repeats is associated with 1 year outcome in patients with ischemic stroke. J Neurol Neurosurg Psychiatry. 2007;78:183–6.PubMedCentralPubMedCrossRef Gromadzka G, Sarzynska-Dlugosz I, Czlonkowska A. IL1RN intron 2 polymorphism caused by variable number tandem repeats is associated with 1 year outcome in patients with ischemic stroke. J Neurol Neurosurg Psychiatry. 2007;78:183–6.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Rafiq S, Stevens K, Hurst AJ, et al. Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels. Genes Immun. 2007;8:344–51.PubMedCrossRef Rafiq S, Stevens K, Hurst AJ, et al. Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels. Genes Immun. 2007;8:344–51.PubMedCrossRef
20.
Zurück zum Zitat Reiner AP, Wurfel MM, Lange LA, et al. Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. Arterioscler Thromb Vasc Biol. 2008;28:1407–12.PubMedCentralPubMedCrossRef Reiner AP, Wurfel MM, Lange LA, et al. Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. Arterioscler Thromb Vasc Biol. 2008;28:1407–12.PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Sims JR, Gharai LR, Schaefer PW, et al. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology. 2009;72:2104–10.PubMedCentralPubMedCrossRef Sims JR, Gharai LR, Schaefer PW, et al. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology. 2009;72:2104–10.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Nicklin MJ, Hughes DE, Barton JL, Ure JM, Duff GW. Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med. 2000;191:303–12.PubMedCentralPubMedCrossRef Nicklin MJ, Hughes DE, Barton JL, Ure JM, Duff GW. Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med. 2000;191:303–12.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Rafiq S, Melzer D, Weedon MN, et al. Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. Diabetologia. 2008;51:2205–13.PubMedCentralPubMedCrossRef Rafiq S, Melzer D, Weedon MN, et al. Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. Diabetologia. 2008;51:2205–13.PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Becker K, Tanzi P, Kalil A, Shibata D, Cain K. Early statin use is associated with increased risk of infection after stroke. J Stroke Cerebrovasc Dis. 2013;22:66–71.PubMedCentralPubMedCrossRef Becker K, Tanzi P, Kalil A, Shibata D, Cain K. Early statin use is associated with increased risk of infection after stroke. J Stroke Cerebrovasc Dis. 2013;22:66–71.PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Montaner J, Chacon P, Krupinski J, et al. Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. Eur J Neurol. 2008;15:82–90.PubMedCrossRef Montaner J, Chacon P, Krupinski J, et al. Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. Eur J Neurol. 2008;15:82–90.PubMedCrossRef
26.
Zurück zum Zitat Emsley HC, Smith CJ, Georgiou RF, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry. 2005;76:1366–72.PubMedCentralPubMedCrossRef Emsley HC, Smith CJ, Georgiou RF, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry. 2005;76:1366–72.PubMedCentralPubMedCrossRef
Metadaten
Titel
Stroke, IL-1ra, IL1RN, Infection and Outcome
verfasst von
Kyra J. Becker
Dorender Dankwa
Richard Lee
Juliane Schulze
Dannielle Zierath
Patricia Tanzi
Kevin Cain
Alexander Dressel
Dean Shibata
Jonathan Weinstein
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Neurocritical Care / Ausgabe 1/2014
Print ISSN: 1541-6933
Elektronische ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-013-9899-x

Weitere Artikel der Ausgabe 1/2014

Neurocritical Care 1/2014 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.