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Effects of pentoxifylline during Schistosoma mansoni infection in Swiss mice: an analysis of worm burden, fecundity and liver histopathology

Published online by Cambridge University Press:  29 January 2010

V.L.T. Mati ,
R.M.C. Freitas  and
A.L. Melo
V.L.T. Mati
Affiliation:
Laboratório de Taxonomia e Biologia de Invertebrados, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
R.M.C. Freitas
Affiliation:
Laboratório de Taxonomia e Biologia de Invertebrados, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
A.L. Melo*
Affiliation:
Laboratório de Taxonomia e Biologia de Invertebrados, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
*
*Fax: +55 31 34092970 E-mail: aldemelo@icb.ufmg.br
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Abstract

The short-term effects of pentoxifylline (PTX) on granulomatous lesions during Schistosoma mansoni infection in Swiss mice were evaluated. Drug administration was initiated 42 and 140 days post-infection (DPI) for the acute and chronic infection groups, respectively. Treatment was carried out daily with 200 mg/kg (subcutaneous route) of the drug for five consecutive days. Recovery of parasites and tissues was performed at 49 DPI and 147 DPI, respectively. Liver histological analysis showed a decrease in the inflammatory reaction and fibrous content of the granulomas studied, and a significant reduction (P < 0.001) in their mean diameter was observed in the groups of rodents treated with PTX in acute and chronic infection, when compared to their respective control groups. However, no alteration in the number of S. mansoni recovered from the portal system was observed, and egg-laying kinetics was not notably modified by PTX treatment, and the immature stage distribution of S. mansoni eggs showed minor intrinsic variations with no statistical differences in the parameter second-stage/female/g among untreated mice and treated mice in acute and chronic infections, respectively, when evaluated by intestinal oograms. Data obtained indicate probable immunomodulatory effects of PTX in murine schistosomiasis both in acute and chronic infection.

Type
Research Papers
Information
Journal of Helminthology , Volume 84 , Issue 4 , December 2010 , pp. 348 - 354
Copyright
Copyright © Cambridge University Press 2010

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References

Amiri, P., Locksley, R.M., Parslow, T.G., Sadick, M., Rector, E., Ritter, D. & McKerrow, J.H. (1992) Tumor necrosis factor α restores granulomas and induces egg-laying in schistosome-infected SCID mice. Nature 356, 604–607.CrossRefGoogle ScholarPubMed
Andrade, Z.A. & Warren, K.S. (1964) Mild prolonged schistosomiasis: alterations in host response with time and the development of portal fibrosis. Transactions of the Royal Society of Tropical Medicine and Hygiene 58, 447–456.Google ScholarPubMed
Bienvenu, J., Doche, C., Gutowski, M.C., Lenoble, M., Lepape, A. & Perdrix, J.P. (1995) Production of proinflammatory cytokines and cytokines involved in the Th1/Th2 balance is modulated by pentoxifylline. Journal of Cardiovascular Pharmacology 25 (Suppl.), 80–84.CrossRefGoogle ScholarPubMed
Calich, V.L.G., Coppi-Vaz, C.A. & Burger, E. (1985) PMN chemotactic factor produced by glass-adherent cells in the acute inflammation caused by Paracoccidiodes brasiliensis. British Journal of Experimental Pathology 66, 57–65.Google Scholar
Carvalho, A.D.V., Alvarenga, R.J. & Melo, A.L. (1986) Histopatologia da esquistossomose mansoni em fígado de Mus musculus infectado por amostras humanas de fase aguda e crônica da periferia de Belo Horizonte, Minas Gerais. Revista da Sociedade Brasileira de Medicina Tropical 19, 89–94.CrossRefGoogle ScholarPubMed
Cheever, A.W., Xu, Y., Macedonia, J.G., Cox, T., Hieny, S. & Sher, A. (1992) The role of cytokines in the pathogenesis of hepatic granulomatous disease in Schistosoma mansoni infected mice. Memórias do Instituto Oswaldo Cruz 87 (Suppl.), 81–85.CrossRefGoogle ScholarPubMed
Cheever, A.W., Poindexter, R.W. & Wynn, T.A. (1999) Egg laying is delayed but worm fecundity is normal in SCID mice infected with Schistosoma japonicum and S. mansoni with or without recombinant tumor necrosis factor alpha treatment. Infection and Immunity 67, 2201–2208.CrossRefGoogle ScholarPubMed
Doenhoff, M., Musallam, R., Bain, J. & McGregor, A. (1978) Studies on the host–parasite relationship in Schistosoma mansoni-infected mice: the immunological dependence of parasite egg excretion. Immunology 35, 771–778.Google ScholarPubMed
El-Lakkany, N. & Nosseir, M. (2007) Pharmacodynamics of pentoxifylline and/or praziquantel in murine schistosomiasis mansoni. Acta Pathologica, Microbiologica et Immunologica Scandinavica 115, 184–194.CrossRefGoogle ScholarPubMed
Goes, A.M., Rezende, S.A., Gazzinelli, G. & Doughty, B.L. (1994) Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. IV. A role for prostaglandin induced inhibition of in vitro granuloma formation. Parasite Immunology 16, 11–18.CrossRefGoogle Scholar
Grzych, J.M., Pearce, E., Cheever, A.W., Caulada, Z.A., Caspar, P., Heiny, S., Lewis, F. & Sher, A. (1991) Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. The Journal of Immunology 146, 1322–1327.CrossRefGoogle ScholarPubMed
Haseeb, M.A., Solomon, W.B. & Palma, J.F. (1996) Schistosoma mansoni: effect of recombinant tumor necrosis factor-α on fecundity and [14C]-tyrosine uptake in females maintained in vitro. Comparative Biochemistry and Physiology 115C, 265–269.Google Scholar
Haseeb, M.A., Sbirazian, D.J. & Preis, J. (2001) Elevated serum levels of TNF-α, sTNF-RI and sTNF-RII in murine schistosomiasis correlate with schistosome oviposition and circumoval granuloma formation. Cytokine 15, 266–269.CrossRefGoogle ScholarPubMed
Henri, S., Chevillard, C., Mergani, A., Paris, P., Gaudart, J., Camila, C., Dessein, H., Montero, F., Elwali, N.E., Saeed, O.K., Magzoub, M. & Dessein, A.J. (2002) Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni: IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation of disease. The Journal of Immunology 169, 929–936.CrossRefGoogle ScholarPubMed
Hermeto, M.V., Bicalho, R.S., Silva, R.E., Melo, A.L. & Pereira, L.H. (1994) Oogram studies in mice infected with Schistosoma mansoni and treated with dexamethasone. Revista do Instituto de Medicina Tropical de São Paulo 36, 99–103.CrossRefGoogle ScholarPubMed
Heyderman, R.S., Klein, N.J., Daramola, O.A. & Levin, M. (1995) Modulation of the endothelial procoagulant response to lipopolysaccharide and tumour necrosis factor-α in vitro: The effects of dexamethasone, pentoxifylline, iloprost and a polyclonal anti-human IL-1α antibody. Inflammation Research 44, 275–280.CrossRefGoogle Scholar
Hoffmann, K.F., Cheever, A.W. & Wynn, T.A. (2000) IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. The Journal of Immunology 164, 6406–6416.CrossRefGoogle ScholarPubMed
Jesus, A.R., Luna, T., Almeida, R.P., Machado, P.R.L. & Carvalho, E.M. (2008) Pentoxifylline down modulates in vitro T cell responses and attenuates pathology in Leishmania and HTLV-I infections. International Immunopharmacology 8, 1344–1353.CrossRefGoogle Scholar
Joseph, A.L. & Boros, D.L. (1993) Tumor necrosis factor plays a role in Schistosoma mansoni egg-induced granulomatous inflammation. The Journal of Immunology 151, 5461–5471.CrossRefGoogle Scholar
Louie, A., Baltch, A.L., Franke, M.A., Ritz, W.J., Smith, R.P., Singh, J.K. & Gordon, M.A. (1996) Effect of pentoxifylline on the course of systemic Candida albicans infection in mice. The Journal of Antimicrobial Chemotherapy 37, 943–954.CrossRefGoogle ScholarPubMed
Marcinkiewicz, J., Grabowska, A., Lauterbach, R. & Bobek, M. (2000) Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages. Immunopharmacology 49, 335–343.CrossRefGoogle ScholarPubMed
Muniz-Junqueira, M.I. (2007) Immunomodulatory therapy associated to anti-parasite drugs as a way to prevent severe forms of malaria. Current Clinical Pharmacology 2, 59–73.CrossRefGoogle ScholarPubMed
Navarro, J., Punzón, M.C., Pizarro, A., Fernández-Cruz, E., Fresno, M. & Muñoz-Fernández, M.A. (1996) Pentoxifylline inhibits acute HIV-1 replication in human T cells by a mechanism not involving inhibition of tumor necrosis factor synthesis or nuclear factor-kappa B activation. AIDS 10, 469–475.CrossRefGoogle ScholarPubMed
Oliveira, T.S., Neto, M.C., Martins, B.J.A., Rodrigues, H.A., Antonino, R.M.P. & Magalhães, A.V. (2000) Action of pentoxifylline on experimental cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis. Memórias do Instituto Oswaldo Cruz 95, 477–482.CrossRefGoogle Scholar
Ostrosky-Zeichner, L., Soto-Hernandez, J.L., Angeles-Morales, V., Teixeira, F., Nava-Ruiz, C., Rios, C., Solis, F. & Sotelo, J. (1996) Effects of pentoxifylline or dexamethasone in combination with amphotericin B in experimental murine cerebral cryptococcosis: evidence of neuroexcitatory pathogenic mechanisms. Antimicrobial Agents and Chemotherapy 40, 1194–1197.CrossRefGoogle ScholarPubMed
Pacheco, L.G.C., Zucconi, E., Mati, V.L.T., Garcia, R.M., Miyoshi, A., Oliveira, S.C., Melo, A.L. & Azevedo, V. (2005) Oral administration of a live Aro attenuated Salmonella vaccine strain expressing 14-kDa Schistosoma mansoni fatty acid-binding protein induced partial protection against experimental schistosomiasis. Acta Tropica 95, 132–142.CrossRefGoogle ScholarPubMed
Pearce, E.J. & MacDonald, A.S. (2002) The immunobiology of schistosomiasis. Nature Reviews Immunology 2, 499–511.CrossRefGoogle ScholarPubMed
Pearce, E.J., Caspar, P., Grzych, J.M., Lewis, F.A. & Sher, A. (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. The Journal of Experimental Medicine 173, 159–166.CrossRefGoogle ScholarPubMed
Pellegrino, J. & Faria, J. (1965) The oogram method for the screening of drugs in schistosomiasis mansoni. American Journal of Tropical Medicine and Hygiene 14, 363–369.CrossRefGoogle ScholarPubMed
Pellegrino, J. & Siqueira, A.F. (1956) Técnica de perfusão para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Revista Brasileira de Malariologia e Doenças Tropicais 8, 589–597.Google Scholar
Pellegrino, J., Oliveira, C.A., Cunha, A.S. & Siqueira, A.F. (1962) New approach to the screening of drugs in experimental schistosomiasis in mice. American Journal of Tropical Medicine and Hygiene 11, 210–215.CrossRefGoogle Scholar
Raso, P.R., Bernardes, C., Tafuri, W.L., Bogliolo, L. & Neves, J. (1978) As dimensões do granuloma causado pelos ovos de Schistosoma mansoni no fígado humano. Revista da Sociedade Brasileira de Medicina Tropical 12, 45–49.CrossRefGoogle Scholar
Reis, L.F., Ventura, T.G., Souza, S.O., Arana-Pino, A., Pelajo-Machado, M., Pereira, M.J.S., Lenzi, H.L., Conceição, M.J. & Takyia, C.M. (2001) Quantitative and qualitative interferences of pentoxifylline on hepatic Schistosoma mansoni granulomas: effects on extracellular matrix and eosinophil population. Memórias do Instituto Oswaldo Cruz 96 (Suppl.), 107–112.CrossRefGoogle ScholarPubMed
Sáez-LIorens, X., Ramilo, O., Mustafá, M.M., Mertsola, J., Alba, C., Hansen, E. & McCracken, G.H. Jr (1990) Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. Antimicrobial Agents and Chemotherapy 34, 837–843.CrossRefGoogle Scholar
Samlaska, C.P. & Winfield, E.A. (1994) Pentoxifylline. Journal of the American Academy of Dermatology 30, 603–621.CrossRefGoogle ScholarPubMed
Sandor, M., Weinstock, J.V. & Wynn, T.A. (2003) Granulomas in schistosome and mycobacterial infections: a model of local immune responses. Trends in Immunology 24, 44–52.CrossRefGoogle Scholar
Seiffge, D., Bissinger, T., Kremer, F., Laux, V. & Schleyrbach, R. (1995) Inhibitory effects of pentoxifylline on LPS-induced leukocyte adhesion and macromolecular extravasation in the microcirculation. Inflammation Research 44, 281–286.CrossRefGoogle ScholarPubMed
Sher, A., Fiorentino, D., Caspar, P., Pearce, E. & Mosmann, T. (1991) Production of IL-10 by CD4+T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. The Journal of Immunology 147, 2713–2716.CrossRefGoogle ScholarPubMed
Silva, L.M., Fernandes, A.L., Barbosa, A. Jr, Oliveira, I.R. & Andrade, Z.A. (2000) Significance of schistosomal granuloma modulation. Memórias do Instituto Oswaldo Cruz 95, 353–361.CrossRefGoogle ScholarPubMed
Tilg, H., Eibl, B., Pichl, M., Gächter, A., Herold, M., Brankova, J., Huber, C. & Niederwieser, D. (1993) Immune response modulation by pentoxifylline in vitro. Transplantation 56, 196–201.CrossRefGoogle ScholarPubMed
Tristão, A.R., Melo, A.L., Vasconcelos, A.C. & Grossi, F.M. (2000) Apoptose na modulação da resposta inflamatória aos ovos do Schistosoma mansoni. Arquivo Brasileiro de Medicina Veterinária e Zootecnia 52, 586–591.CrossRefGoogle Scholar
Valadares, T.E., Coelho, P.M.Z., Pellegrino, J. & Sampaio, I.B.M. (1981) Schistosoma mansoni: aspectos da oviposição da cepa LE em camundongos infectados com um casal de vermes. Revista do Instituto de Medicina Tropical de São Paulo 23, 6–11.Google Scholar
Wanchu, A., Bhatnagar, A., Kumar, B., Bambery, P. & Singh, S. (2003) Reduced apoptosis by pentoxiphylline among patients with HIV infection. International Immunopharmacology 3, 359–364.CrossRefGoogle ScholarPubMed
Ward, A. & Clissold, S. (1987) Pentoxifylline – a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 34, 50–97.CrossRefGoogle ScholarPubMed
Xiong, L.J., Zhu, J.F. & Luo, D.D. (2003) Effects of pentoxifylline on the hepatic content of TGF-β1 and collagen in Schistosomiasis japonica mice with liver fibrosis. World Journal of Gastroenterology 9, 152–154.CrossRefGoogle ScholarPubMed