PMID: 8596047Mar 1, 1996Paper

The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites

The Journal of Immunology : Official Journal of the American Association of Immunologists
P GadangiB N Cronstein

Abstract

The anti-inflammatory mechanism of sulfasalazine is not well understood. It has recently been shown that sulfasalazine inhibits 5-aminoimidazole-4-carboxamidoribonucleotide (AICAR) transformylase, an enzyme involved in de novo purine biosynthesis. We recently demonstrated that methotrexate promotes intracellular AICAR accumulation, thereby increasing adenosine release and diminishing inflammation, so we tested the hypothesis that sulfasalazine similarly promotes intracellular AICAR accumulation. We studied adenosine release and the state of inflammation in in vitro and in vivo models of the inflammatory process. The adhesion of stimulated neutrophils (FMLP) to endothelial cells preincubated with sulfasalazine was inhibited in a dose-dependent manner. Elimination of extracellular adenosine by addition of adenosine deaminase or inhibition of adenosine by the adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) completely reversed the anti-inflammatory effect of sulfasalazine (at concentrations <1 microM in this in vitro model. To determine whether this phenomenon was relevant to inhibition of inflammation in vivo, we studied the effect of sulfasalazine (100 mg/kg/day by gastric gavage for 3 days) on leukocyte ...Continue Reading

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