Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation
Konstantin Prass, Christian Meisel, Conny Höflich, Johann Braun, Elke Halle, Tilo Wolf, Karsten Ruscher, Ilya V Victorov, Josef Priller, Ulrich Dirnagl, Hans-Dieter Volk, Andreas Meisel, Konstantin Prass, Christian Meisel, Conny Höflich, Johann Braun, Elke Halle, Tilo Wolf, Karsten Ruscher, Ilya V Victorov, Josef Priller, Ulrich Dirnagl, Hans-Dieter Volk, Andreas Meisel
Abstract
Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
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References
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