Monocytes are major players in the prognosis and risk of infection after acute stroke

Abstract

[Background and Purpose]: Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (S AI) 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-α, IFN-γ, 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-a 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-α 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. © 2009 American Heart Association, Inc.This work was supported by a grant from the Fundación de Investigaciones Científicas (PI06/0909), and the partial support of the Fundación Melchor Colet. Xabier Urra and Álvaro Cervera are recipients of grants from Instituto Carlos III, Spanish Ministry of Health.Peer Reviewe