IL-6 is a predictive biomarker for stroke associated infection and future mortality in the elderly after an ischemic stroke

Experimental Gerontology

Volumn 48, Issue 9, 2013, Pages 960-965

  Kwan, Joseph ^a   Horsfield, Gill ^b   Bryant, Timothy ^b   Gawne Cain, Mary ^b   Durward, Giles ^c   Byrne, Christopher D ^d   Englyst, Nicola A ^d  

^a BOURNEMOUTH UNIVERSITY   (United Kingdom)

^b UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

^c UK   (United Kingdom)

^d UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Biomarker; IL 6; Infection; Mortality; Risk factors; Stroke

Indexed keywords

INTERLEUKIN 6;

AGED; ARTICLE; BLOOD LEVEL; BRAIN ISCHEMIA; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DISEASE MARKER; DISEASE SEVERITY; ELDERLY CARE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; INFECTION; MAJOR CLINICAL STUDY; MALE; MORTALITY; OUTCOME ASSESSMENT; PATIENT ASSESSMENT; PNEUMONIA; PREDICTION; PRIORITY JOURNAL; PROTEIN DETERMINATION; RISK ASSESSMENT; RISK FACTOR; STROKE ASSOCIATED INFECTION;

95% CIS; 95% CONFIDENCE INTERVALS; BARTHEL INDEX; BI; BIOMARKER; BLOOD PRESSURE; BMI; BODY MASS INDEX; BP; COMPUTED TOMOGRAPHY; CT; HPAA; HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; IL-6; INFECTION; MODIFIED RANKIN SCORE; MORTALITY; MRS; NATIONAL INSTITUTE OF HEALTH STROKE SCORE; NIHSS; ODDS RATIOS; OR; RISK FACTORS; SAI; STROKE; STROKE ASSOCIATED INFECTION;

AGED; AGED, 80 AND OVER; BIOLOGICAL MARKERS; BRAIN ISCHEMIA; ENGLAND; FEMALE; HUMANS; INFLAMMATION; INTERLEUKIN-6; MALE; MIDDLE AGED; OPPORTUNISTIC INFECTIONS; PNEUMONIA; PROGNOSIS; RETROSPECTIVE STUDIES; RISK FACTORS; SEVERITY OF ILLNESS INDEX; STROKE;

EID: 84881095918     PISSN: 05315565     EISSN: 18736815     Source Type: Journal    
DOI: 10.1016/j.exger.2013.07.003     Document Type: Article

References (48)

1. Bamford J., Sandercock P., Dennis M., Burn J., Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991, 337:1521-1526.
2. Biswas P., Delfanti F., Bernasconi S., Mengozzi M., Cota M., Polentarutti N., Mantovani A., Lazzarin A., Sozzani S., Poli G. Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. Blood 1998, 91:258-265.
3. Braun J.S., Prass K., Dirnagl U., Meisel A., Meisel C. Protection from brain damage and bacterial infection in murine stroke by the novel caspase-inhibitor Q-VD-OPH. Exp. Neurol. 2007, 206:183-191.
4. Brett F.M., Mizisin A.P., Powell H.C., Campbell I.L. Evolution of neuropathologic abnormalities associated with blood-brain barrier breakdown in transgenic mice expressing interleukin-6 in astrocytes. J. Neuropathol. Exp. Neurol. 1995, 54:766-775.
5. Brott T., Adams H.P., Olinger C.P., Marler J.R., Barsan W.G., Biller J., Spilker J., Holleran R., Eberle R., Hertzberg V. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989, 20:864-870.
6. Cesari M., Penninx B.W., Newman A.B., Kritchevsky S.B., Nicklas B.J., Sutton-Tyrrell K., Rubin S.M., Ding J., Simonsick E.M., Harris T.B., Pahor M. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 2003, 108:2317-2322.
7. Chamorro A., Amaro S., Vargas M., Obach V., Cervera A., Torres F., Planas A.M. Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke. J. Neurol. Neurosurg. Psychiatry 2006, 77:1279-1281.
8. Chamorro A., Amaro S., Vargas M., Obach V., Cervera A., Gomez-Choco M., Torres F., Planas A.M. Catecholamines, infection, and death in acute ischemic stroke. J. Neurol. Sci. 2007, 252:29-35.
9. Chamorro A., Urra X., Planas A.M. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke 2007, 38:1097-1103.
10. Clark J., Vagenas P., Panesar M., Cope A.P. What does tumour necrosis factor excess do to the immune system long term?. Ann. Rheum. Dis. 2005, 64(Suppl. 4):iv70-iv76.
11. Davenport R.J., Dennis M.S., Wellwood I., Warlow C.P. Complications after acute stroke. Stroke 1996, 27:415-420.
12. Emsley H.C., Hopkins S.J. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurol. 2008, 7:341-353.
13. Emsley H.C., Smith C.J., Gavin C.M., Georgiou R.F., Vail A., Barberan E.M., Hallenbeck J.M., del Zoppo G.J., Rothwell N.J., Tyrrell P.J., Hopkins S.J. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J. Neuroimmunol. 2003, 139:93-101.
14. Emsley H.C., Smith C.J., Hopkins S.J. Infection and brain-induced immunodepression after acute ischemic stroke. Stroke 2008, 39:e7.
15. Englyst N.A., Horsfield G., Kwan J., Byrne C.D. Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity. J. Cereb. Blood Flow Metab. 2008, 28:1196-1203.
16. Fassbender K., Dempfle C.E., Mielke O., Rossol S., Schneider S., Dollman m., Hennerici M. Proinflammatory cytokines: indicators of infection in high-risk patients. J. Lab. Clin. Med. 1997, 130:535-539.
17. Haeusler K.G., Schmidt W.U., Fohring F., Meisel C., Helms T., Jungehulsing G.J., Nolte C.H., Schmolke K., Wegner B., Meisel A., Dirnagl U., Villringer A., Volk H.D. Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans. Cerebrovasc. Dis. 2008, 25:50-58.
18. Harms H., Prass K., Meisel C., Klehmet J., Rogge W., Drenckhahn C., Gohler J., Bereswill S., Gobel U., Wernecke K.D., Wolf T., Arnold G., Halle E., Volk H.D., Dirnagl U., Meisel A. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS One 2008, 3:e2158.
19. Harms H., Reimnitz P., Bohner G., Werich T., Klingebiel R., Meisel C., Meisel A. Influence of stroke localization on autonomic activation, immunodepression, and post-stroke infection. Cerebrovasc. Dis. 2011, 32:552-560.
20. Johansson T., Olsson B., Carlberg K., Karlsson M., Fagerlund M. Hypercortisolism after stroke - partly cytokine-mediated?. J. Neurol. Sci. 1997, 147:43-47.
21. Johnston K.C., Li J.Y., Lyden P.D., Hanson S.K., Feasby T.E., Adams R.J., Faught R.E., Haley E.C. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke 1998, 29:447-453.
22. Klehmet J., Harms H., Richter M., Prass K., Volk H.D., Dirnagl U., Meisel A., Meisel C. Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience 2009, 158:1184-1193.
23. Kwan J., Hand P. Infection after acute stroke is associated with poor short-term outcome. Acta Neurol. Scand. 2007, 115:331-338.
24. Kwan J., Pickering R.M., Kunkel D., Fitton C., Jenkinson D., Perry V.H., Ashburn A.M. Impact of stroke-associated infection on long-term survival: a cohort study. J. Neurol. Neurosurg. Psychiatry 2013, 84:297-304.
25. Langhorne P., Stott D.J., Robertson L., MacDonald J., Jones L., McAlpine C., Dick F., Taylor G.S., Murray G. Medical complications after stroke: a multicenter study. Stroke 2000, 31:1223-1229.
26. Mahoney F.I., Barthel D.W. Functional evaluation: the Barthel Index. Md. State Med. J. 1965, 14:61-65.
27. Marz P., Cheng J.G., Gadient R.A., Patterson P.H., Stoyan T., Otten U., Rose-John S. Sympathetic neurons can produce and respond to interleukin 6. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:3251-3256.
28. Miller L.S., Pietras E.M., Uricchio L.H., Hirano K., Rao S., Lin H., O'Connell R.M., Iwakura Y., Cheung A.L., Cheng G., Modlin R.L. Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J. Immunol. 2007, 179:6933-6942.
29. Nederkoorn P.J., Westendorp W.F., Hooijenga I.J., de Haan R.J., Dippel D.W., Vermeij F.H., Dijkgraaf M.G., Prins J.M., Spanjaard L., van de Beek D. Preventive antibiotics in stroke study: rationale and protocol for a randomised trial. Int. J. Stroke 2011, 6:159-163.
30. Patel M.D., Coshall C., Rudd A.G., Wolfe C.D. Cognitive impairment after stroke: clinical determinants and its associations with long-term stroke outcomes. J. Am. Geriatr. Soc. 2002, 50:700-706.
31. Perini F., Morra M., Alecci M., Galloni E., Marchi M., Toso V. Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients. Neurol. Sci. 2001, 22:289-296.
32. Prass K., Meisel C., Hoflich C., Braun J., Halle E., Wolf T., Ruscher K., Victorov I.V., Priller J., Dirnagl U., Volk H.D., Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J. Exp. Med. 2003, 198:725-736.
33. Ramadori G., Christ B. Cytokines and the hepatic acute-phase response. Semin. Liver Dis. 1999, 19:141-155.
34. Schlosser H.G., Volk H.D., Splettstosser G., Brock M., Woiciechowsky C. A new qualitative interleukin-6 bedside test can predict pneumonia in patients with severe head injury - comparison to the standard Immulite test and a semiquantitative bedside test. J. Neurosurg. Anesthesiol. 2007, 19:5-9.
35. Smith C.J., Emsley H.C., Gavin C.M., Georgiou R.F., Vail A., Barberan E.M., del Zoppo G.J., Hallenbeck J.M., Rothwell N.J., Hopkins S.J., Tyrrell P.J. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol. 2004, 4:2.
36. Smith C.J., Emsley H.C., Vail A., Georgiou R.F., Rothwell N.J., Tyrrell P.J., Hopkins S.J. Variability of the systemic acute phase response after ischemic stroke. J. Neurol. Sci. 2006, 251:77-81.
37. Szczudlik A., Dziedzic T., Bartus S., Slowik A., Kieltyka A. Serum interleukin-6 predicts cortisol release in acute stroke patients. J. Endocrinol. Invest. 2004, 27:37-41.
38. Urra X., Cervera A., Obach V., Climent N., Planas A.M., Chamorro A. Monocytes are major players in the prognosis and risk of infection after acute stroke. Stroke 2009, 40:1262-1268.
39. van Swieten J.C., Koudstaal P.J., Visser M.C., Schouten H.J., van G.J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988, 19:604-607.
40. Vargas M., Horcajada J.P., Obach V., Revilla M., Cervera A., Torres F., Planas A.M., Mensa J., Chamorro A. Clinical consequences of infection in patients with acute stroke: is it prime time for further antibiotic trials?. Stroke 2006, 37:461-465.
41. Vogelgesang A., Grunwald U., Langner S., Jack R., Broker B.M., Kessler C., Dressel A. Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke 2008, 39:237-241.
42. Waje-Andreassen U., Krakenes J., Ulvestad E., Thomassen L., Myhr K.M., Aarseth J., Vedeler C.A. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol. Scand. 2005, 111:360-365.
43. Wang H.E., Shapiro N.I., Griffin R., Safford M.M., Judd S., Howard G. Inflammatory and endothelial activation biomarkers and risk of sepsis: a nested case-control study. J Crit Care 2013, (in press, pii: S0883-9441(12)00437-6). 10.1016/j.jcrc.2012.11.002.
44. Wartenberg K.E., Stoll A., Funk A., Meyer A., Schmidt J.M., Berrouschot J. Infection after acute ischemic stroke: risk factors, biomarkers, and outcome. Stroke Res. Treat. 2011, 830614.
45. Westendorp W.F., Nederkoorn P.J., Vermeij J.D., Dijkgraaf M.G., van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011, 11:110.
46. Whiteley W., Jackson C., Lewis S., Lowe G., Rumley A., Sandercock P., Wardlaw J., Dennis M., Sudlow C. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med. 2009, 6:e1000145.
47. Whiteley W., Jackson C., Lewis S., Lowe G., Rumley A., Sandercock P., Wardlaw J., Dennis M., Sudlow C. Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study. Stroke 2011, 42:10-16.
48. Whiteley W., Wardlaw J., Dennis M., Lowe G., Rumley A., Sattar N., Welsh P., Green A., Andrews M., Sandercock P. The use of blood biomarkers to predict poor outcome after acute transient ischemic attack or ischemic stroke. Stroke 2012, 43:86-91.