Importance of TNF-α in the course of acute infection with Trypanosoma cruzi : influence of its inhibition by pentoxifylline treatment

• Published in: Memórias do Instituto Oswaldo Cruz 2008-02, Vol.103 (1), p.21-26
• Main Authors: Andrade, Sonia G, Magalhães, Lorena dos Anjos, Pessina, Daniel Huber
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Chagas Disease - drug therapy; Chagas Disease - immunology; Chagas Disease - pathology; Immunohistochemistry; Mice; Mice, Inbred C3H; necrosis; Necrosis - drug therapy; Parasitemia - drug therapy; Parasitemia - immunology; PARASITOLOGY; pentoxifylline; Pentoxifylline - pharmacology; spleen; Spleen - pathology; Splenic Diseases - drug therapy; Splenic Diseases - pathology; Time Factors; TNF-alpha; TROPICAL MEDICINE; Trypanosoma cruzi; Trypanosoma cruzi - necrosis - spleen - TNF-α - pentoxifylline; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1678-8060; 0074-0276; 1678-8060
• DOI: 10.1590/S0074-02762008005000006

Infection of C3H/He mice with the Peruvian strain of Trypanosoma cruzi (Biodeme type I, Z2b), a macrophagotropic strain, determined severe parasitism of macrophages, necrosis of the spleen, and high host mortality. In the present study, pentoxifylline (PTX), an inhibitor of TNF-α was investigated on its action upon splenic necrosis, parasitemia and host survival. Immunohistochemical data suggested the importance of this cytokine in parasite destruction and decreasing of parasitemia, although paradoxically contributing to the high mortality of infected mice. Necrotic lesions involving several organs, specially the heart, in acute Chagas disease, are important aggravating factors, increasing cardiac morbidity. Advantage of inhibiting TNF-α action was herein investigated. Infected mice were divided into two groups: untreated (n = 24), and PTX treated mice (n = 25). PTX was administered in two daily doses of 30 mg/kg/bw, by intraperitoneal route. Normal controls either treated with PTX or saline were also included. Histopathology of the spleen and in situ immunolabeling of TNF-α, using anti-TNF-α monoclonal antibody, were performed. Necrotic areas were evaluated by morphometry. Mice treated with PTX showed a significant decrease of necrotic areas and diminution of TNF-α expression in spleen tissue, suggesting that PTX treatment could control TNF-α effects, and thus be used as an adjuvant in the treatment of acute Chagas' disease.