TY - JOUR
T1 - CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression
AU - Wang, Ruoxiang
AU - Fang, Qiding
AU - Zhang, Liying
AU - Radvany, Laszlo
AU - Sharma, Ajay
AU - Noben-Trauth, Nancy
AU - Mills, Gordon B.
AU - Shi, Yufang
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 1997/3/15
Y1 - 1997/3/15
N2 - The pathogenesis of septic shock is due mainly to bacterial toxin stimulation of the immune system, resulting in an excessive production of proinflammatory cytokines. TNF-α has been implicated as a major mediator in septic shock. Coinjection of D-galactosamine and LPS or staphylococcal enterotoxin B induced a rapid-onset, low-dose form of septic shock syndrome and ultimately led to death. We found that both the septic shock syndrome and death could be prevented by administration of anti-CD28 Ab. The protection induced by anti-CD28 Ab was associated with a decrease in TNF-α levels in the circulation. In addition, serum from anti-CD28 Ab-treated mice was capable of inhibiting the production of TNF-α by bone marrow-derived macrophages following treatment with LPS, indicating that anti-CD28 Ab induced production of soluble factors that subsequently inhibited the production of TNF-α. We confirmed that one of the factors present in serum was IL-10, because anti-CD28 Ab treatment stimulated the expression of IL-10, both in splenocytes and in T cell lines. Furthermore, injection of anti-IL-10 Abs could abolish the protective effect of anti-CD28 Ab on septic shock. Anti-IL-10 Ab could also suppress the anti-CD28 Ab-induced inhibition of TNF-α production, either in vivo or in vitro. Thus, we conclude that ligation of CD28 induces expression of IL-10, which in turn suppresses TNF-α production and prevents septic shock.
AB - The pathogenesis of septic shock is due mainly to bacterial toxin stimulation of the immune system, resulting in an excessive production of proinflammatory cytokines. TNF-α has been implicated as a major mediator in septic shock. Coinjection of D-galactosamine and LPS or staphylococcal enterotoxin B induced a rapid-onset, low-dose form of septic shock syndrome and ultimately led to death. We found that both the septic shock syndrome and death could be prevented by administration of anti-CD28 Ab. The protection induced by anti-CD28 Ab was associated with a decrease in TNF-α levels in the circulation. In addition, serum from anti-CD28 Ab-treated mice was capable of inhibiting the production of TNF-α by bone marrow-derived macrophages following treatment with LPS, indicating that anti-CD28 Ab induced production of soluble factors that subsequently inhibited the production of TNF-α. We confirmed that one of the factors present in serum was IL-10, because anti-CD28 Ab treatment stimulated the expression of IL-10, both in splenocytes and in T cell lines. Furthermore, injection of anti-IL-10 Abs could abolish the protective effect of anti-CD28 Ab on septic shock. Anti-IL-10 Ab could also suppress the anti-CD28 Ab-induced inhibition of TNF-α production, either in vivo or in vitro. Thus, we conclude that ligation of CD28 induces expression of IL-10, which in turn suppresses TNF-α production and prevents septic shock.
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M3 - Article
C2 - 9058822
AN - SCOPUS:0031569098
SN - 0022-1767
VL - 158
SP - 2856
EP - 2861
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -