Published online before print November 29, 2007, doi: 10.1161/STROKEAHA.107.502898
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(Stroke. 2008;39:e8.)
© 2008 American Heart Association, Inc.
Letters to the Editor |
Response to Letter by Emsley et al
Institute of Neurosciences, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
Institute for Biomedical Research (IIBB)-Spanish Research Council (CSIC), IDIBAPS, Barcelona, Spain
Response:
We appreciate Dr Emsley and colleagues’ attention to our recent review of the immunological changes that supervene after acute ischemic brain injury.1 Their study describing a reduction of cytokine production by endotoxin-stimulated whole blood from stroke patients relative to controls is of clinical interest because the magnitude of the suppression was inversely correlated with stroke severity and outcome, although weakly correlated with infarct volume.2 If validated in further studies the amount of cytokine production after endotoxin stimulation of whole blood ex vivo could be a test assisting at the bed side for the early prediction of clinical outcome after stroke. However, this finding is in apparent conflict with observations made by previous investigators describing after stroke a long-lasting production of several cytokines by peripheral blood cells.3 Unraveling this controversy is of major relevance because it would help to clarify the relative contribution of the ischemic brain and peripheral blood cells to the plasma elevation of cytokines, as previously confirmed in numerous studies. Emsley and colleagues offer several methodological and analytical reasons to justify their previously unrecognized findings. However, the diverse clinical criteria and the modest size of these studies could also explain the apparent discrepancies. Thus, Emsley et al disqualified in their study patients that showed any improvement in symptoms after hospital admission. Alternatively, Ferrarese and colleagues excluded the patients with signs of acquired infection after stroke admission. Based on our previous research, these criteria likely are of major significance because the plasma levels of several cytokines are different in patients with early stroke worsening,4,5 or in patients who develop an infection early after stroke.6 To what extent these criteria played a role in the British and Italian studies is difficult to foresee.
Emsley and colleagues also affirm in their letter that poststroke infection is in itself an important independent contributor to poor outcome although we have previously posited that this conclusion is premature.7 Indeed, recent prospective studies did not find in multivariate analysis an independent association between infection and stroke worsening.8,9 Contrarily, in many instances early infection after stroke may represent a marker of a large infarction, and whose apparent deleterious clinical effect is confounded by stronger stressors such as larger lesions, or more frequent use of invasive maneuvers. In summary, only appropriately sized studies that include stroke subjects with assorted clinical course and stroke subtypes, and subjects with poststroke complications such as urinary infection or pneumonia will be able to decipher the multiple uncertainities still remaining in the complex cytokine cascade after acute ischemic stroke. The value of whole blood stimulation after stroke must be replicated in additional studies although these tests must contemplate the possibility that different peripheral white cells such as lymphocytes, monocytes, and neutrophils might also show a diverse behavior after stimulation.
Acknowledgments
Disclosures
None.
References
1. Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007; 38: 1097–1103.
2. Emsley HCA, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurology. 2007; 7: 5.[CrossRef][Medline] [Order article via Infotrieve]
3. Ferrarese C, Mascarucci P, Zoia C, Cavarretta R, Frigo M, Begni B, Sarinella F, Frattola L, De Simoni MG. Increased cytokine release from peripheral blood cells after acute stroke. J Cereb Blood Flow Metab. 1999; 19: 1004–1009.[CrossRef][Medline] [Order article via Infotrieve]
4. Vila N, Castillo J, Dávalos A, Chamorro A. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke. 2000; 31: 2325–2329.
5. Vila N, Castillo J, Davalos A, Esteve A, Planas AM, Chamorro A. Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke. Stroke. 2003; 34: 671–675.
6. Chamorro A, Amaro S, Vargas M, Obach V, Cervera A, Torres F, Planas AM. Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke J Neurol Neurosurg Psychiatry. 2006; 77: 1279–1281.
7. Vargas M, Horcajada JP, Obach V, Revilla M, Cervera A, Torres F, Planas AM, 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.
8. Aslanyan CJ, Weir CJ, Dienerc HC, Kaste M, Lees KR; for the GAIN International Steering Committee and Investigator. Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary analysis of the GAIN International trial. Eur J Neurol. 2004; 11: 49–53.[CrossRef][Medline] [Order article via Infotrieve]
9. Dziewas R, Ritter M, Schilling M, Konrad C, Oelenberg S, Nabavi DG, Stogbauer F, Ringelstein EB, Ludemann P. Pneumonia in acute stroke patients fed by nasogastric tube. J Neurol Neurosurg Psychiatry. 2004; 75: 852–856.
Related Article:
Stroke 2008 39: e7.
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