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Title
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Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-cd3 monoclonal-antibody in mice by interleukin-10
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Author
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Abstract
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| Since IL-10 was recently shown to inhibit several T cell functions in vitro, we investigated the effects of IL-10 on the cytokine release syndrome induced in mice by the 145-2C11 anti-CD3 mAb. As OKT3 in man, this mAb induces a massive polyclonal T cell activation before to induce immunosuppression. First, we found that administration of 1000 U of recombinant mouse IL-10 (mIL-10) 30 min before injection of 10 pg of the 145-2C11 antimouse CD3 mAb markedly reduced the systemic release of IFN-gamma and TNF. in contrast, IL-IO pretreatment did not significantly modify the release of IL-6. To determine the effect of IL-10 pretreatment on the endogenous secretion of IL-10 induced by the 145-2C11 mAb, mice were injected with human IL-10 (hIL-10) which does not cross-react in the ELISA for mIL-10 determination. While hIL-10 was as efficient as mIL-10 in reducing TNF and IFN-gamma release, it did not modify peak serum levels of IL-10. The modulation of cytokine production by mIL-10 was associated with a significant reduction of the toxicity of the 145-2C11 mAb, as assessed by the attenuation of hypothermia and by the reduced lethality in D-galactosamine-sensitized mice. We conclude that IL-10 differentially regulates the in vivo production of cytokines and decreases the systemic toxicity induced by the 145-2C11 mAb. These observations suggest potential therapeutic applications of IL-10 in organ transplantation, especially in association with anti-CD3 mAb. |
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Language
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English
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Source (journal)
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Transplantation. - Baltimore, Md, 1963, currens
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Publication
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Baltimore, Md
:
1994
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ISSN
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0041-1337
1534-6080
[online]
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DOI
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10.1097/00007890-199405270-00005
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Volume/pages
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57
:10
(1994)
, p. 1436-1439
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ISI
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A1994NP05700005
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Full text (Publisher's DOI)
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