Benznidazole, a drug employed in the treatment of Chagas´disease, down regulates the synthesis of nitrite and cytokines by murine stimulated macrophages

REVELLI S; LE PAGE C; PIAGGIO E; WIETZERBIN J; BOTTASSO O; BOTTASSO OSCAR

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 1999 vol. 118 p. 271 - 277

0009-9104

Benznidazole (BZL) is a nitroheterocyclic drug employed in the chemotherapy of Chagas? disease, a protozoan disease caused by Trypanosoma cruzi. Because this parasite mostly replicates in macrophages, we investigated whether BZL was likely to modify the synthesis of macrophage mediators such as nitrite, tumour necrosis factor-alpha (TNF-a), IL-1b, IL-6 and IL-10. Control and stimulated murine macrophages (lipopolysaccharide (LPS) and/or interferon-gamma (IFN-g)) were treated with BZL and measurements were carried out in culture supernatants collected 24 h later. Synthesis of nitrite, IL-6 and IL-10 was maximal upon combined stimulation with LPSþIFN-g, whereas lower amounts of the threemediators were detected when both stimuli were given alone. BZL treatment significantly reduced nitrite, IL-6 and IL-10 production, to undetectable levels in some cases, particularly IL-6 and IL-10. LPS was the most potent stimulus of IL-1b and TNF-a production, followed by LPSþIFN-g and IFN-g in decreasing order. BZL partly inhibited TNF-a synthesis, but this effect was smaller than that observed for nitrite, IL-6 and IL-10. LPS-induced production of IL-1b was also affected by BZL. Semiquantification of gene expression for inducible nitric oxide synthase (iNOS) showed that BZL completely inhibited iNOS gene induction by IFN-g, and resulted in respective inhibitions of 30% and 50% with LPS- and LPSþIFN-g-stimulated cells. BZL was not cytotoxic on macrophage cultures, asshown by the lactate dehydrogenase activity. Besides its trypanocidal activity, BZL may also alter the balance between pro- and anti-inflammatory mediators with important consequences for the course of T. cruzi infection.