Sulphasalazine inhibits macrophage activation: Inhibitory effects on inducible nitric oxide synthase expression, interleukin-12 production and major histocompatibility complex II expression

György Haskó, Csaba Szabó, Zoltán H. Németh, Edwin A. Deitch

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Abstract

The anti-inflammatory agent sulphasalazine is an important component of several treatment regimens in the therapy of ulcerative colitis, Crohn's disease and rheumatoid arthritis. Sulphasalazine has many immunomodulatory actions, including modulation of the function of a variety of cell types, such as lymphocytes, natural killer cells, epithelial cells and mast cells. However, the effect of this agent on macrophage (Mφ) function has not been characterized in detail. In the present study, we investigated the effect of sulphasalazine and two related compounds - sulphapyridine and 5-aminosalicylic acid - on Mφ activation induced by bacterial lipopolysaccharide (LPS) and interferon-γ (IFN-γ). In J774 Mφ stimulated with LPS (10 μg/ml) and IFN-γ (100 U/ml), sulphasalazine (50-500 μM) suppressed nitric oxide (NO) production in a concentration-dependent manner. The expression of the inducible NO synthase (iNOS) was suppressed by sulphasalazine at 500 μM. Sulphasalazine inhibited the LPS/IFN-γ-induced production of both interleukin-12 (IL-12) p40 and p70. The suppression of both NO and IL-12 production by sulphasalazine was superior to that by either sulphapyridine or 5-aminosalicylic acid. Although the combination of LPS and IFN-γ induced a rapid expression of the active forms of p38 and p42/44 mitogen-activated protein kinases and c-Jun terminal kinase, sulphasalazine failed to interfere with the activation of any of these kinases. Finally, sulphasalazine suppressed the IFN-γ-induced expression of major histocompatibility complex class II. These results demonstrate that the Mφ is an important target of the immunosuppressive effect of sulphasalazine.

Original languageEnglish
Pages (from-to)473-478
Number of pages6
JournalImmunology
Volume103
Issue number4
DOIs
Publication statusPublished - Aug 23 2001

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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