title: Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.
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.
authors.affiliation: Department of Experimental Neurology, Charité Hospital, Humboldt University, Schumannstrasse 20-21, D-10098 Berlin, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Prass
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Conny
authors.initials: C
authors.lastname: Höflich
authors.forename: Johann
authors.initials: J
authors.lastname: Braun
authors.forename: Elke
authors.initials: E
authors.lastname: Halle
authors.forename: Tilo
authors.initials: T
authors.lastname: Wolf
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Victorov
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001424:Bacterial Infections / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D002546:Ischemic Attack, Transient / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011433:Propranolol / Q000494:pharmacology; D020521:Stroke / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D011433:Propranolol