Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-CD3 monoclonal antibody in mice by interleukin-10

V Donckier, V Flament, C Gérard, D Abramowicz, P Vandenabeele, M Wissing, A Delvaux, W Fiers, O Leo, T Velu

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 micrograms of the 145-2C11 antimouse CD3 mAb markedly reduced the systemic release of IFN-gamma and TNF. In contrast, IL-10 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-sensitize 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.

Original languageEnglish
Pages (from-to)1436-1439
Number of pages4
JournalTransplantation
Volume57
Issue number10
Publication statusPublished - 1994

Keywords

  • Animals
  • Antibodies, Monoclonal
  • CD3 Complex
  • Cyclosporine
  • Female
  • Interferon-gamma
  • Interleukin-10
  • Interleukin-6
  • Mice
  • Mice, Inbred BALB C
  • Secretory Rate
  • Shock
  • T-Lymphocytes
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-CD3 monoclonal antibody in mice by interleukin-10'. Together they form a unique fingerprint.

Cite this