Title
Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-cd3 monoclonal-antibody in mice by interleukin-10 Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-cd3 monoclonal-antibody in mice by interleukin-10
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Human medicine
Source (journal)
Transplantation. - Baltimore, Md, 1963, currens
Volume/pages
57(1994) :10 , p. 1436-1439
ISSN
0041-1337
ISI
A1994NP05700005
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
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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