The Journal of Experimental Medicine
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Published online 25 August 2003 doi:10.1084/jem.20021098
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© Rockefeller University Press, 0022-1007/2003/9/725 $5.00
The Journal of Experimental Medicine, Volume 198, Number 5, 725-736

Stroke-induced Immunodeficiency Promotes Spontaneous Bacterial Infections and Is Mediated by Sympathetic Activation Reversal by Poststroke T Helper Cell Type 1–like Immunostimulation

Konstantin Prass1,2, Christian Meisel3, Conny Höflich3, Johann Braun1,2, Elke Halle4, Tilo Wolf2, Karsten Ruscher1, Ilya V. Victorov5, Josef Priller1,2, Ulrich Dirnagl1, Hans-Dieter Volk3 and Andreas Meisel1,2

1 Department of Experimental Neurology, Charité, Humboldt University, 10098 Berlin, Germany
2 Department of Neurology, Charité, Humboldt University, 10098 Berlin, Germany
3 Department of Medical Immunology, Charité, Humboldt University, 10098 Berlin, Germany
4 Department of Microbiology, Charité, Humboldt University, 10098 Berlin, Germany
5 Brain Research Institute, Academy of Medical Sciences, 103064 Moscow, Russian Federation

Address correspondence to Christian Meisel, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, OX3 7BN Oxford, United Kingdom. Phone: 44-1865-287538; Fax: 44-1865-287533; email: chr.meisel{at}charite.de; or Ulrich Dirnagl, Department of Neurology, Charité Hospital, Humboldt University, Schumannstraße 20-21, D-10098 Berlin, Germany. Phone: 49-30-450-560184; Fax: 49-30-450-560915; email: ulrich.dirnagl{at}charite.de

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 ß-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.

Key Words: T lymphocytes • natural killer cells • interferon {gamma} • pneumonia • brain ischemia


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