Concanavalin A-induced Hepatitis in mice is prevented by interleukin (IL)-10 and exacerbated by endogenous IL-10 deficiency

Roberto Di Marco, Ming Xiang, Paola Zaccone, Camilla Leonardi, Sabrina Franco, Pierluigi Meroni, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

One single intra-venous (i.v.) injection of Concanavalin A (Con A) into mice provokes a cell-mediated immunoinflammatory hepatitis. We have presently evaluated the immunopharmacological effects of exogenous interleukin (IL)-10 and the role of endogenous IL-10 in this model by using exogenous IL-10, anti-IL-10 monoclonal antibody (mAb) and mice with disrupted IL-10 gene (IL-10 KO mice). Whilst exogenous IL-10 administered in a prophylactic (1 h prior to Con A) and even 'early' therapeutic fashion (30 min after Con A) reduced the elevation of transaminase activities in plasma in a dose-dependent manner, observed in control mice, these biochemical markers of liver injury were significantly increased both in IL-10 KO mice as well as in those receiving anti-IL-10 mAb. Interestingly, doses of Con A lower than 20 mg/kg that were only capable of inducing slight serological signs of hepatitis in mice, exerted marked hepatitic effects when administered to either anti-IL-10 mAb-treated mice or to IL-10 KO mice. The disease modulating effects of exogenous IL-10 and either genetical or pharmacologically-induced IL-10 deficiency were associated with profound and opposite modifications of the Con A-induced increase in the circulating levels of IFN-γ and TNF-α. Relative to control animals, the blood levels of these cytokines were diminished in IL-10-treated mice and augmented in both IL-10 KO mice and anti-IL-10 mAb-treated mice. These results prove the physiological antiinflammatory role of endogenous IL-10 in Con A induced hepatitis and the beneficial effects of IL-10 treatment to prevent this condition.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalAutoimmunity
Volume31
Issue number2
Publication statusPublished - 1999

Keywords

  • Cytokines
  • Hepatitis
  • Immunotherapy
  • Interleukin-10

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Di Marco, R., Xiang, M., Zaccone, P., Leonardi, C., Franco, S., Meroni, P., & Nicoletti, F. (1999). Concanavalin A-induced Hepatitis in mice is prevented by interleukin (IL)-10 and exacerbated by endogenous IL-10 deficiency. Autoimmunity, 31(2), 75-83.