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The inhibitory effect of pentamidine on the production of chemotactic cytokines by in vitro stimulated human blood cells

Inflammation Research volume 45, pages 357–363 (1996)Cite this article

Abstract

Pentamidine is an antiprotozoal drug with additional antiinflammatory activities that are not well understood. We now report that pentamidine inhibited the human whole blood production of the chemotactic cytokines (chemokines) interleukin (IL)-8, growth related gene α (GROα) and monocyte chemotactic protein-1 (MCP-1). The title compound dose-dependently suppressed the lipopolysaccharide (LPS)- and phytohemagglutinin (PHA)-stimulated whole blood generation of these chemokines with IC50-values of 2.1 and 2.2 μM (IL-8), 2.4 and 1.8 μM (GROα) and 2.8 and 2.4 μM (MCP-1). The inhibition was specific: when tested at 10 μM, pentamidine had no significant inhibitory effect on the PHA-induced generation of the non-chemotactic cytokines tumor necrosis factor-α (TNF-α), IL-1β, IL-2, IL-4, IL-5, IL-10 and interferon-ψ (IFN-ψ), except for a partial inhibition on IL-6. Time course experiments indicated that pentamidine (10 μM) retained its ability to inhibit PHA-stimulated IL-8 production even when its addition was delayed for up to 24 h after mitogen stimulation. Furthermore, reverse transcription PCR studies showed that pentamidine had no effect on IL-8 mRNA expression. These finding indicate that pentamidine is a posttranscription acting inhibitor of human chemokine production. This activity may contribute to the antiinflammatory action ascribed to the title compound.

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Author information

Affiliations

  1. Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium

    J. Van Wauwe, F. Aerts & H. Van Genechten

  2. Innogenetics, Industriepark Zwijnaarde, B-9052, Gent, Belgium

    H. Blockx, W. Deleersnijder & H. Walter

Authors
  1. J. Van Wauwe
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  2. F. Aerts
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  3. H. Van Genechten
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  4. H. Blockx
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  5. W. Deleersnijder
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  6. H. Walter
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accepted by M. J. Parnham

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Van Wauwe, J., Aerts, F., Van Genechten, H. et al. The inhibitory effect of pentamidine on the production of chemotactic cytokines by in vitro stimulated human blood cells. Inflamm Res 45, 357–363 (1996). https://doi.org/10.1007/BF02252949

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  • DOI: https://doi.org/10.1007/BF02252949

Key words

  • Pentamidine
  • Interleukin-8
  • Chemokine