Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.
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.
Prass
Konstantin
K
Department of Experimental Neurology, Charité Hospital, Humboldt University, Schumannstrasse 20-21, D-10098 Berlin, Germany.
Meisel
Christian
C
Höflich
Conny
C
Braun
Johann
J
Halle
Elke
E
Wolf
Tilo
T
Ruscher
Karsten
K
Victorov
Ilya V
IV
Priller
Josef
J
Dirnagl
Ulrich
U
Volk
Hans-Dieter
HD
Meisel
Andreas
A
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*
D011433:Propranolol