Publication
Title
Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-cd3 monoclonal-antibody in mice by interleukin-10
Author
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.
Language
English
Source (journal)
Transplantation. - Baltimore, Md, 1963, currens
Publication
Baltimore, Md : 1994
ISSN
0041-1337
1534-6080 [online]
Volume/pages
57:10(1994), p. 1436-1439
ISI
A1994NP05700005
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Project info
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 06.01.2015
Last edited 01.12.2017