Regulation of the inflammatory response to Staphylococcus aureus-induced brain abscess by interleukin-10.
A characteristic of brain abscess is a localized suppurative infection leading to substantial damage of the adjacent central nervous system tissue. The orchestrated interplay of pro- and antiinflammatory cytokines released by leukocytes as well as resident cells of the central nervous system is crucial for both an effective host defense and for limiting tissue damage in brain abscess. To study the regulatory role of interleukin (IL)-10 in brain abscess in vivo, IL-10-deficient (IL-10(0/0)) mice were stereotaxically infected with Staphylococcus aureus-laden agarose beads. Increased numbers of intracerebral (IC) granulocytes, macrophages, CD4+ and CD8+ T cells, and higher levels of TNF, IL-1beta, and iNOS were observed in IL-10(0/0) mice than in wild-type mice, whereas chemokines were induced earlier and more pronounced in wild-type mice. Together with prominent microvascular hemorrhage, necrotic vasculitis, severe brain edema, and markedly increased abscess size, these alterations led to an increased morbidity of IL-10(0/0) mice. Nevertheless, the hyperinflammatory response of IL-10(0/0) mice did not improve bacterial elimination. Collectively, these data outline the important role of IL-10 in vivo for the regulation of the IC host immune response in experimental S. aureus-induced brain abscess.
Stenzel
Werner
W
Abteilung für Neuropathologie, Universität zu Köln, Köln, Germany. w.stenzel@uni-koeln.de
Dahm
Julia
J
Sanchez-Ruiz
Monica
M
Miletic
Hrvoje
H
Hermann
Manuel
M
Courts
Cornelius
C
Schwindt
Heinrich
H
Utermöhlen
Olaf
O
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001922:Brain Abscess / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000235:genetics; D015169:Colony Count, Microbial; D003199:Computer Systems; D016207:Cytokines / Q000235:genetics; D004660:Encephalitis / Q000382:microbiology*; D016753:Interleukin-10 / Q000378:metabolism*; D007700:Kinetics; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D013211:Staphylococcus aureus
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10