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Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

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Helminthologia

Summary

The effect of amphotericin B colloidal dispersion (ABCD) on selected immunological parameters and growth of the larval cysts in mice infected intraperitoneally with Echinococcus multilocularis protoscoleces was observed. ABCD was administered at a dose 10 mg/kg body weight twice a week from week 5 to 10 post infection (p.i.). The Echinococcus infection suppressed the proliferative response of splenic T lymphocytes to nonspecific mitogen concanavalin A throughout almost the whole course of the experiment and ABCD administration did not affect this inhibittion. The increase in the proliferative response of B lymphocytes to lipopolysaccharide was found in infected mice with ABCD treatment from week 6 to 10 p.i. ABCD induced a significant rise of the splenic CD4 T cell subpopulation in infected mice only on week 6 p.i. The CD8 T subpopulation was not influenced by the therapy. The level of serum Th1 cytokine IFN-γ in infected and ABCD treated mice was elevated only at week 8 p.i., while the level of serum Th2 cytokine IL-5 was not influenced by the therapy. The ABCD treatment inhibited the IFN-γ production by splenocytes in vitro from week 6 to 10 p.i. On the contrary, the IL-5 production in vitro was stimulated at weeks 8 and 12 p.i. None antiparasitic effect of ABCD on larval growth was determined.

Results suggest that amphotericin B colloidal dispersion did not affect the inhibited Th1 immune response after parasite infection. On the contrary, ABCD advanced the Th2 immune response development, which allows the progressive growth of the parasite.

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References

  • Abbas, A. K., Murphy, K. M., Sher, A. (1996): Functional diversity of helper T lymphocytes. Nature, 383: 787–793

    Article  PubMed  CAS  Google Scholar 

  • Abu-Salah, K. M. (1996): Amphotericin B: an update. Brit. J. Biomed. Sci., 53: 122–133

    CAS  Google Scholar 

  • Ammann, R. W., Eckert, J. (1996): Cestodes: Echinococcus. Gastroenter. Clin. North Am., 25: 655–689

    Article  CAS  Google Scholar 

  • Borošková, Z., Dvorožňáková, E., Ševčíková, Z. (2003): Cellular immune reactions of mice with alveolar echinococcosis after albendazole therapy. Helminthologia, 40: 187–194

    Google Scholar 

  • Brajtburg, J., Bolard, J. (1996): Carrier effects on biological activity of amphotericin B. Clin. Microb. Rev., 9: 512–531

    CAS  Google Scholar 

  • Brajtburg, J., Powderly, W. G., Kobayashi, G. S., Medoff, G. (1990): Amphotericin B: current understanding of mechanisms of action. Antimicrob. Agents Chemother., 34: 183–188

    PubMed  CAS  Google Scholar 

  • Bresson-Hadni, S., Liance, A., Meyer, J. P., Houin, R., Bresson, J. L., Vuitton, D. A. (1990): Cellular immunity in experimental Echinococcus multilocularis infection. II. Sequental and comparative phenotypic study of the periparasitic mononuclear cells in resistant and sensitive mice. Clin. Exp. Immunol., 82: 378–383

    Article  PubMed  CAS  Google Scholar 

  • Capece, B. P., Navarro, M., Arcalis, T., Castells, G., Toribio, L., Perez, F., Carretero, A., Ruberte, J., Arboix, M., Cristofol, C. (2003): Albendazole sulphoxide enantiomers in pregnant rats’ embryo concentrations and developmental toxicity. Vet. J., 165: 266–275

    Article  PubMed  CAS  Google Scholar 

  • Christiansen, K. J., Bernard, E. M., Gold, J. W. M., Armstrong, D. (1985): Distribution and activity of amphotericin B in humans. J. Infect. Dis., 152: 1037–1043

    PubMed  CAS  Google Scholar 

  • Clements, J. S. Jr., Peacock, J. E. Jr. (1990): Amphotericin B revisited: reassessment of toxicity. Amer. J. Med., 88: 22–27

    Google Scholar 

  • Clemons, K. V., Sobel, R. A., Williams, P. L., Stevens, D. A. (2001): Comparative toxicities and pharmacokinetics of intrathecal lipid (amphotericin B colloidal dispersion) and conventional deoxycholate formulations of amphotericin B in rabbits. Antimicrob. Agents Chemother., 45: 612–615

    Article  PubMed  CAS  Google Scholar 

  • Dvorožňáková, E., Hrčková, G., Borošková, Z., Velebný, S., Dubinský, P. (2004): Effect of treatment with free and liposomized albendazole on selected immunological parameters and cyst growth in mice infected with Echinococcus multilocularis. Parasitol. Int., 53: 315–325

    Article  PubMed  CAS  Google Scholar 

  • Ehrenfreund-Kleinman, T., Domb, A. J., Jaffe, C. L., Nasereddin, A., Leshem, B., Golenser, J. (2005): The effect of amphotericin b derivatives on Leishmania and immune functions. J. Parasitol., 91: 158–163

    Article  PubMed  CAS  Google Scholar 

  • Ellis, D. (2002): Amphotericin B: spectrum and resistance. J. Antimicrob. Chemother., 49: 7–10

    Article  PubMed  CAS  Google Scholar 

  • Emery, I., Liance, M., Deriaud, E., Vuitton, D. A., Houin, E., Leclerc, C. (1996): Characterization of T-cell immune responses of Echinococcus multilocularis-infected. Parasite. Immunol., 18: 463–472

    PubMed  CAS  Google Scholar 

  • Geginat, G., Kretschmar, M., Walter, S., Junker, D., Hof, H., Nichterlein, T. (1999): Suppression of acquired immunity against Listeria monocytogenes by amphotericin B-mediated inhibition of CD8 T cell function. J. Infect. Dis., 180: 1186–1194

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, B. E., Wyde, P. R., Willson, S. Z. (1992): Aerosolized liposomal amphotericin B liposomes for treatment of pulmonary and systematic Cryptococcus neoformans infections in mice. Antimicrob. Agents Chemother., 36: 1466–1471

    PubMed  CAS  Google Scholar 

  • Gottstein, B., Haag, K., Walker, M., Matsumoto, J., Mejri, N., Hemphill, A. (2006): Molecular survival strategies of Echinococcus multilocularis in the murine host. Parasitol. Int., 55: S45–S49

    Article  PubMed  CAS  Google Scholar 

  • Hann, I. M., Prentice, H. G. (2001): Lipid-based amphotericin B: a review of the last 10 years of use. Int. J. Antimicrob. Agents, 17: 161–169

    Article  PubMed  CAS  Google Scholar 

  • Heath, D. D. (1995): Immunology of Echinococcus infection. In Thompson, R. C. A., Lymbery, A. J. (Eds): Echinococcus and hydatid disease. CAB INTERNATIONAL, Wallingford, UK: 183–199

    Google Scholar 

  • Hiemenz, J. W., Walsh, T. J. (1996): Lipid formulations of amphotericin B: recent progress and future directions. Clin. Infect. Dis., 22: S133–S144

    PubMed  CAS  Google Scholar 

  • Hrčková, G., Velebný, S. (1997): Effect of praziquantel and liposome-incorporated praziquantel on peritoneal macrophage activation in mice infected with Mesocestoides corti tetrathyridia (Cestoda). Parasitology, 114: 475–482

    Article  PubMed  Google Scholar 

  • Inselmann, G., Volkmann A., Heidemann, H. T. (2000): Comparison of the effects of liposomal amphotericin B and conventional amphotericin B on propafenone metabolism and hepatic cztochrome P.450 in rats. Antimicrob. Agents Chemother., 44:131–133

    Article  PubMed  CAS  Google Scholar 

  • Janknegt, R., DeMarie, S., Bakker-Woudenberg, I. A., Crommelin D. J. (1992): Liposomal and lipid formulations of amphotericin B. Clin. Pharmacokinet., 23: 279–291

    PubMed  CAS  Google Scholar 

  • Joly, V., Farinotti, R., Saint-Julien, L., Chéron, M., Carbon, C., Zeni, P. (1994): In vitro renal toxicity and in vivo therapeutic efficacy in experimental murine cryptococcosis of amphotericin B (Fungizone) associated with intralipid. Antimicrob. Agents Chemother., 38: 177–183

    PubMed  CAS  Google Scholar 

  • Karyotakis, N. C., Anaissie, E. J. (1994): Efficacy of escalating doses of liposomal amphotericin B (AmBisome) against hematogenous Candida lusitaniae and Candida krusei infection in neutropenic mice. Antimicrob. Agents Chemother., 38: 2660–2662

    PubMed  CAS  Google Scholar 

  • Kilwinski, J., Jenne, L., Jellen-Ritter, A., Radloff, P., Flick, W., Kern, P. (1999): T lymphocyte cytokine profile at a single cell level in alveolar echinococcosis. Cytokine, 11: 373–381

    Article  PubMed  CAS  Google Scholar 

  • Kizaki, T., Kobayashi, S., Ogasawara, K., Day, N. K., Good, R. A., Onoe, K. (1991): Immune suppression induced by protoscoleces of E. multilocularis in mice. Evidence for the presence of CD8dull suppressor cells in spleens of mice intraperitoneally infected with E. multilocularis. J. Immunol., 147: 1659–1666

    PubMed  CAS  Google Scholar 

  • Manfras, B. J., Reuter, S., Wendland, T., Boehm, B. O., Kern, P. (2004): Impeded Th1 CD4 memory T cell generation in chronic-persisting liver infection with Echinococcus multilocularis. Int. Immunol., 16: 43–50

    Article  PubMed  CAS  Google Scholar 

  • Murray, H. W. (2005): Prevention of relapse after chemotherapy in a chronic intracellular infection: mechanisms in experimental visceral leishmaniasis. J. Immunol., 174: 4916–4923

    PubMed  CAS  Google Scholar 

  • Pagé, M., Bajaouni, N., Ciqo-Mars, B., Lemieux, P. (1988): Optimization the tetrazolium based colorimetric assay for the measurement of cell number and cytotoxicity. Int. J. Immunopharmacol., 10: 785–793

    Article  PubMed  Google Scholar 

  • Pérez-Serrano, J., Denegri, G., Casado, N., Rodríguez-Caabeiro, F. (1997): In vivo effect of oral albendazole and albendazole sulphoxide on development of secondary Echinococcosis in mice. Int. J. Parasitol., 27: 1341–1345

    Article  PubMed  Google Scholar 

  • Persat, F., Bouhours, J. F., Mojon, M., Petavy, A. F. (1990): Analysis of the monohexosylceramide fraction of Echinococcus multilocularis metacestodes. Mol. Biochem. Parasitol., 41: 1–6

    Article  PubMed  CAS  Google Scholar 

  • Rama-Iniguez, S., Dea-Ayuela, M. A., Sanchez-Brunete J. A., Torrado, J. J., Alunda, J. M., Bolas-Fernandez, F. (2006): Real-time reverse transcription-PCR quantification of cytokine mRNA expression in golden Syrian hamster infected with Leishmania infantum and treated with a new amphotericin B formulation. Antimicrob. Agents Chemother., 50: 1195–1201

    Article  PubMed  CAS  Google Scholar 

  • Resch, K. (1999): Cytokines. In Nijkamp F. P., Parnham, M. J. (Eds): Principles of Immunopharmacology. Birghäuser Verlag, Basel, Boston, Berlin: 53–81

    Google Scholar 

  • Reuben, J. M, Tanner, C. E. (1983): Protection against experimental echinococcosis by non-specifically stimulated peritoneal cells. Parasite Immunol., 5: 61–66

    PubMed  CAS  Google Scholar 

  • Reuter, S., Jensen, B., Buttenschoen, K., Kratzer, W., Kern, P. (2000): Benzimidazoles in the treatment of alveolar echinococcosis: a comparative study and review of the literature. J. Antimicrob. Chemother., 46: 451–456

    Article  PubMed  CAS  Google Scholar 

  • Reuter, S., Merkle, M., Brehm, K., Kern, P., Manfras, B. (2003a): Effect of amphotericin B on larval growth of Echinococcus multilocularis. Antimicrob. Agents Chemother., 47: 620–625

    Article  PubMed  CAS  Google Scholar 

  • Reuter, S., Buck, A., Grebe, O., Nussle-Kugele, K., Kern, P., Manfras, B. J. (2003b): Salvage treatment with amphotericin B in progressive human alveolar echinococcosis. Antimicrob. Agents Chemother., 47: 3586–3591

    Article  PubMed  CAS  Google Scholar 

  • Rigano, R., Profumo, E., Buttari, B., Teggi, A., Siracusano, A. (1999): Cytokine gene expression in peripheral blood mononuclear cells (PBMC) from patients with pharmacologically treated cystic echinococcosis. Clin. Exp. Immunol., 118: 95–101

    Article  PubMed  CAS  Google Scholar 

  • Sau, K., Mambula, S. S., Latz, E., Henneke, P., Golenbock, D. T., Levitz, S. M. (2003): The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor-and CD14-dependent mechanism. J. Biol. Chem., 278: 37561–37568

    Article  PubMed  CAS  Google Scholar 

  • Schantz, P. M. (2002): Progress and challenges in biology, treatment and control of echinococcosis. Abstracts ICOPA X, Vancouver, Canada: 243

  • Schindler, J. J., Warren, R. P., Allen, S. D., Jackson, M. K. (1993): Immunological effects of amphotericin B and liposomal amphotericin B on splenocytes from immune-normal and compromised mice. Antimicrob. Agents Chemother, 37: 2716–2721

    PubMed  CAS  Google Scholar 

  • Simitsopoulou, M., Roilides, E., Dotis, J., Dalakiouridou, M., Dudkova, A. F., Andreadou, E., Walsh, T. J. (2005): Differential expression of cytokines and chemokines in human monocytes induced by lipid formulations of amphotericin B. Antimicrob. Agents Chemother., 49: 1397–1403

    Article  PubMed  CAS  Google Scholar 

  • Stein, S. H., Little, J. R., Little, K. D. (1987): Parallel inheritance of tissue catalase activity and immunostimulatory action of amphotericin B in inbred mouse strains. Cell. Immunol., 105: 99–109

    Article  PubMed  CAS  Google Scholar 

  • Sturm, D., Menzel, J., Gottstein, B., Kern, P. (1995): Interleukin-5 is the predominant cytokine produced by peripheral blood mononuclear cells in alveolar echinococcosis. Infect. Immun., 63: 1688–1697

    PubMed  CAS  Google Scholar 

  • Šoltýs, J., Quinn, M. T. (1999): Modulation of endotoxin-and enterotoxin-induced cytokine release by in vivo treatment with β-(1,6)-branched β-(1,3)-glucan. Infect. Immun., 67: 244–252

    PubMed  Google Scholar 

  • Šoltýs, J., Turčeková, L.’, Rycke, de P. H. (1999): The effect Echinococcus hydatid cyst fluid and protoscoleces on mouse peritoneal macrophages and spleen lymphocytes. Helminthologia, 36: 25–30

    Google Scholar 

  • Thompson, R. C. A. (1995): Biology and systematics of Echinococcus. In Thompson, R. C. A., Lymbery, A. J. (Eds): Echinococcus and hydatid disease. CAB INTERNATIONAL, Wallingford, UK: 1–50

    Google Scholar 

  • Vuitton, D. A. (2003): The ambiguous role of immunity in Echinococcosis: protection of the host or of the parasite? Acta. Trop., 85: 119–132

    Article  PubMed  CAS  Google Scholar 

  • Vuitton, D. A., Zhang, S. L., Yang, Y., Godot, V., Beurton, I., Mantion, G., Bresson-Hadni, S. (2006): Survival strategy of Echinococcus multilocularis in the human host. Parasitol. Int., 55: S51–S55

    Article  PubMed  CAS  Google Scholar 

  • Vuitton, D. A. (1999): New trends in the treatment of echinococcosis. Helminthologia, 36: 167–170

    Google Scholar 

  • Wolf, J. E., Massof, S. E. (1990): In vivo activation of macrophage oxidative burst activity by cytokines and amphotericin B. Infect. Immun., 58:1296–1300

    PubMed  CAS  Google Scholar 

  • Yardley, V., Croft, S. L. (1999): In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections. Am. J. Trop. Med. Hyg., 61: 193–197

    PubMed  CAS  Google Scholar 

  • Zhang, Z., Lipman, J. M., Diener, R. M., Thomas, P. (2006): Comparative immunotoxicity evaluation of amphotericin B and ABELCET, an amphotericin B lipid complex (ABLC). Int. J. Toxicol., 25: 487–492

    Article  PubMed  CAS  Google Scholar 

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Porubcová, J., Dvorožňáková, E. & Ševčíková, Z. Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion. Helminthologia 44, 47–56 (2007). https://doi.org/10.2478/s11687-007-0003-y

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