Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells: Implications for multiple sclerosis

Marco Cosentino, Mauro Zaffaroni, Marco Ferrari, Franca Marino, Raffaella Bombelli, Emanuela Rasini, Gianmario Frigo, Angelo Ghezzi, Giancarlo Comi, Sergio Lecchini

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon (IFN)-γ plays a pivotal role in the pathogenesis of multiple sclerosis (MS), while IFN-β may be able to modify the clinical course of the disease, eventually also by counterbalancing IFN-γ-mediated effects. Catecholamines (CA) exert important effects on the immune response, both as transmitters between the nervous and the immune system, as well as autocrine/paracrine mediators in immune cells, and several lines of evidence support their involvement in MS. In particular, dysregulated production of CA seems to occur in peripheral blood mononuclear cells (PBMCs) of MS patients. We assessed the effects of IFN-β and IFN-γ on endogenous CA in PBMCs. In cultured PBMCs stimulated with phytohaemagglutinin (PHA), IFN-β increased CA production and induced CA release in the culture medium, while IFN-γ decreased both CA production and the expression of mRNA for the CA-synthesizing enzyme tyrosine hydroxylase. Coincubation with both IFNs prevented the inhibitory effect of IFN-γ, as well as the stimulatory effect of IFN-β. IFNs are the first physiological compounds shown to affect endogenous CA in PBMCs: in view of the role of CA-dependent mechanisms in the immune response, these findings may help to better understand the mechanisms of action of IFN-β as an immunomodulatory drug in MS.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalJournal of Neuroimmunology
Volume162
Issue number1-2
DOIs
Publication statusPublished - May 2005

Keywords

  • Endogenous catecholamines
  • Interferon-β
  • Interferon-γ
  • Multiple sclerosis
  • Peripheral blood mononuclear cells
  • Phytohaemagglutinin
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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