Divergent effects of interleukin-4 and interferon-γ on macrophage- derived chemokine production: An amplification circuit of polarized T helper 2 responses

Raffaella Bonecchi, Silvano Sozzani, Johnny T. Stine, Walter Luini, Giovanna D'Amico, Paola Allavena, David Chantry, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFNγ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time- dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells.

Original languageEnglish
Pages (from-to)2668-2671
Number of pages4
JournalBlood
Volume92
Issue number8
Publication statusPublished - Oct 15 1998

ASJC Scopus subject areas

  • Hematology

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