Title
Systemic release and protective role of il-10 in staphylococcal-enterotoxin b-induced shock in mice Systemic release and protective role of il-10 in staphylococcal-enterotoxin b-induced shock in mice
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Human medicine
Source (journal)
The journal of immunology. - Baltimore, Md
Volume/pages
153(1994) :6 , p. 2618-2623
ISSN
0022-1767
ISI
A1994PF18900027
Carrier
E
Target language
English (eng)
Abstract
Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that induces the production of several pro-inflammatory cytokines, leading to a self-limited shock. In the present study, we show that SEB also triggers the systemic release of IL-10, an anti-inflammatory and immunosuppressive cytokine. Serum IL-10 was undetectable (<1000 pg/ml) in control BALB/c mice and rose to 8500 +/- 2850 pg/ml (mean +/- SEM) 4 h after injection of 100 mu g SEB. Cell depletion experiments and analysis of IL-10 mRNA expression indicated that CD4(+) cells played a major role in SEB-induced IL-10 production. Pretreatment of mice with neutralizing anti-IL-10 mAb before SEB challenge did not modify the release of TNF but led to increased and sustained IL-2 and IFN-gamma serum levels. Furthermore, although no lethality occurred in mice injected with SEB and control mAb, injection of anti-IL-10 mAb before SEB resulted in a 30% lethality (p < 0.05). This lethality was completely prevented by anti-IFN-gamma mAb injection, indicating that IFN-gamma plays a crucial role in the increased toxicity of SEB in anti-IL-10 mAb-injected mice. We conclude that SEB induces the production of IL-10 by CD4(+) cells in vivo and that endogenous IL-10 plays an important immunoregulatory role in this model by down-regulating IL-2 and IFN-gamma production.
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