BACKGROUND AND PURPOSE: Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (SAI) or severe stroke. Whether changes in monocytes are related to specific effects, or simply mark brain damage, remains unsettled. METHODS: We used flow cytometry in 45 consecutive strokes and 12 healthy controls to assess the time course of monocytes, their phenotype, and the production of cytokines after stimulation. Cortisol, TNF-alpha, IFN-gamma, and IL-10 were measured in serum and metanephrine in plasma. The effects of humoral and cellular parameters on the risk of SAI and poor outcome were tested in multivariate analyses adjusted for confounders (NIHSS score, age, and tube feeding). RESULTS: Surface expression of human leukocyte antigen-DR, Toll-like receptor-2, and production of TNF-alpha in monocytes were independently associated with stroke. Distinct immune mechanisms were related with functional outcome and the risk of SAI; the signature of SAI included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced production of TNF-alpha in monocytes; poor outcome was associated with increased expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47). SAI did not predict poor outcome (OR, 5.63; 95% CI, 0.45-70.42; P=0.18). CONCLUSIONS: In human stroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke.
BACKGROUND AND PURPOSE: Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (SAI) or severe stroke. Whether changes in monocytes are related to specific effects, or simply mark brain damage, remains unsettled. METHODS: We used flow cytometry in 45 consecutive strokes and 12 healthy controls to assess the time course of monocytes, their phenotype, and the production of cytokines after stimulation. Cortisol, TNF-alpha, IFN-gamma, and IL-10 were measured in serum and metanephrine in plasma. The effects of humoral and cellular parameters on the risk of SAI and poor outcome were tested in multivariate analyses adjusted for confounders (NIHSS score, age, and tube feeding). RESULTS: Surface expression of humanleukocyte antigen-DR, Toll-like receptor-2, and production of TNF-alpha in monocytes were independently associated with stroke. Distinct immune mechanisms were related with functional outcome and the risk of SAI; the signature of SAI included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced production of TNF-alpha in monocytes; poor outcome was associated with increased expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47). SAI did not predict poor outcome (OR, 5.63; 95% CI, 0.45-70.42; P=0.18). CONCLUSIONS: In humanstroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke.
Authors: Ángel Chamorro; Andreas Meisel; Anna M Planas; Xabier Urra; Diederik van de Beek; Roland Veltkamp Journal: Nat Rev Neurol Date: 2012-06-05 Impact factor: 42.937
Authors: Sarah Hoffmann; Hendrik Harms; Lena Ulm; Darius G Nabavi; Bruno-Marcel Mackert; Ingo Schmehl; Gerhard J Jungehulsing; Joan Montaner; Alejandro Bustamante; Marcella Hermans; Frank Hamilton; Jos Göhler; Uwe Malzahn; Carolin Malsch; Peter U Heuschmann; Christian Meisel; Andreas Meisel Journal: J Cereb Blood Flow Metab Date: 2016-10-14 Impact factor: 6.200
Authors: Grant C O'Connell; Madison B Treadway; Connie S Tennant; Noelle Lucke-Wold; Paul D Chantler; Taura L Barr Journal: Transl Stroke Res Date: 2018-03-17 Impact factor: 6.829
Authors: Antje Vogelgesang; Verena E L May; Uwe Grunwald; Maren Bakkeboe; Soenke Langner; Henry Wallaschofski; Christof Kessler; Barbara M Bröker; Alexander Dressel Journal: PLoS One Date: 2010-01-14 Impact factor: 3.240