CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression

Ruoxiang Wang, Qiding Fang, Liying Zhang, Laszlo Radvany, Ajay Sharma, Nancy Noben-Trauth, Gordon Mills, Yufang Shi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2856-2861
Number of pages6
JournalJournal of Immunology
Volume158
Issue number6
StatePublished - Mar 15 1997
Externally publishedYes

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Bacterial Toxins
Septic Shock
Interleukin-10
Ligation
Galactosamine
Serum
Immune System
Macrophages
Cytokines
T-Lymphocytes
Cell Line
Injections
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Wang, R., Fang, Q., Zhang, L., Radvany, L., Sharma, A., Noben-Trauth, N., ... Shi, Y. (1997). CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression. Journal of Immunology, 158(6), 2856-2861.

CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression. / Wang, Ruoxiang; Fang, Qiding; Zhang, Liying; Radvany, Laszlo; Sharma, Ajay; Noben-Trauth, Nancy; Mills, Gordon; Shi, Yufang.

In: Journal of Immunology, Vol. 158, No. 6, 15.03.1997, p. 2856-2861.

Research output: Contribution to journalArticle

Wang, R, Fang, Q, Zhang, L, Radvany, L, Sharma, A, Noben-Trauth, N, Mills, G & Shi, Y 1997, 'CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression', Journal of Immunology, vol. 158, no. 6, pp. 2856-2861.
Wang R, Fang Q, Zhang L, Radvany L, Sharma A, Noben-Trauth N et al. CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression. Journal of Immunology. 1997 Mar 15;158(6):2856-2861.
Wang, Ruoxiang ; Fang, Qiding ; Zhang, Liying ; Radvany, Laszlo ; Sharma, Ajay ; Noben-Trauth, Nancy ; Mills, Gordon ; Shi, Yufang. / CD28 Ligation Prevents Bacterial Toxin-Induced Septic Shock in Mice by Inducing IL-10 Expression. In: Journal of Immunology. 1997 ; Vol. 158, No. 6. pp. 2856-2861.
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