Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice

Ming Xiang, Paola Zaccone, Roberto Di Marco, Gaetano Magro, Maurizio Di Mauro, Barbara Beltrami, Pierluigi Meroni, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

Rolipram is a type IV phosphodiesterase inhibitor endowed with powerful immunomodulatory properties. In this study, we evaluated the effects of this drug on the development of the T-cell-mediated hepatitis inducible in mice by concanavalin A. The results indicated that prophylactic treatment with either 5 or 10 mg/kg rolipram injected intraperitoneally 24 h and 1 h prior to intravenous (i.v.) challenge with 20 mg/kg concanavalin A successfully ameliorated serological and histological signs of liver damage, so that the treated mice showed lower transaminase levels in the plasma and milder mononuclear cell infiltration of the liver as compared to vehicle-treated controls. Moreover, this effect was associated with profound modifications of circulating levels of cytokines released after concanavalin A injection, with the blood levels of interferon-γ and tumor necrosis factor-α being significantly lower and those of interleukin-10 higher than those of the control mice. In particular, the increased blood levels of interleukin-10 might play an important role in the anti-hepatitic effects of rolipram as coadministering this compound with anti-interleukin-10 monoclonal antibody significantly reduced its anti-inflammatory action. These results suggest that rolipram may be useful in the clinical setting for the treatment of cell-mediated immunoinflammatory diseases such as immunoinflammatory hepatitis. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)399-404
Number of pages6
JournalEuropean Journal of Pharmacology
Volume367
Issue number2-3
DOIs
Publication statusPublished - Feb 19 1999

Keywords

  • Concanavalin A
  • Cytokine
  • Hepatitis
  • Immunotherapy
  • Interleukin-10
  • Rolipram

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint Dive into the research topics of 'Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice'. Together they form a unique fingerprint.

  • Cite this

    Xiang, M., Zaccone, P., Di Marco, R., Magro, G., Di Mauro, M., Beltrami, B., Meroni, P., & Nicoletti, F. (1999). Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice. European Journal of Pharmacology, 367(2-3), 399-404. https://doi.org/10.1016/S0014-2999(98)00901-7