BACKGROUND & AIMS: Hepatic alveolar echinococcosis (AE), caused by the larval growth of Echinococcus multilocularis, is one of the most lethal helminthic diseases with no satisfactory treatment. Advances in the understanding of the host's immune response (Th2 responses associated with a progressive form of AE), have driven the research towards immune stimulation as an alternative possibility to treat patients. We previously reported clinical stabilization associated with a shift from a Th2 to a Th1 cytokine profile in an AE patient treated with interferon (IFN)alpha. METHODS: The effects of recombinant IFN alpha-2a were analyzed in the susceptible C57BL/6J E. multilocularis infected mice. Parasitic burden, macrophage functions, and specific T-cell responses were studied 15, 45, and 90 days postinfection. RESULTS: After 90 days postinfection, 75% of infected IFN alpha-2a-treated mice had no hepatic lesions and half were fully protected. IFN alpha-2a treatment markedly decreased the abnormally elevated production of IL-10 in both spleen cell cultures and peritoneal macrophage cultures from infected mice and restored phagocytosis and oxidative metabolism of macrophages. It also inhibited IL-6 and IL-13 antigen-induced secretions in spleen cell cultures. CONCLUSIONS: Through its immunoregulatory properties, IFN alpha-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.
BACKGROUND & AIMS:Hepatic alveolar echinococcosis (AE), caused by the larval growth of Echinococcus multilocularis, is one of the most lethal helminthic diseases with no satisfactory treatment. Advances in the understanding of the host's immune response (Th2 responses associated with a progressive form of AE), have driven the research towards immune stimulation as an alternative possibility to treat patients. We previously reported clinical stabilization associated with a shift from a Th2 to a Th1 cytokine profile in an AE patient treated with interferon (IFN)alpha. METHODS: The effects of recombinant IFN alpha-2a were analyzed in the susceptible C57BL/6J E. multilocularis infected mice. Parasitic burden, macrophage functions, and specific T-cell responses were studied 15, 45, and 90 days postinfection. RESULTS: After 90 days postinfection, 75% of infected IFN alpha-2a-treated mice had no hepatic lesions and half were fully protected. IFN alpha-2a treatment markedly decreased the abnormally elevated production of IL-10 in both spleen cell cultures and peritoneal macrophage cultures from infected mice and restored phagocytosis and oxidative metabolism of macrophages. It also inhibited IL-6 and IL-13 antigen-induced secretions in spleen cell cultures. CONCLUSIONS: Through its immunoregulatory properties, IFN alpha-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.
Authors: Bruno Gottstein; Matthias Wittwer; Marc Schild; Michael Merli; Stephen L Leib; Norbert Müller; Joachim Müller; Rolf Jaggi Journal: PLoS One Date: 2010-04-01 Impact factor: 3.240
Authors: Stefan Reuter; Andreas Buck; Olaf Grebe; Karin Nüssle-Kügele; Peter Kern; Burkhard J Manfras Journal: Antimicrob Agents Chemother Date: 2003-11 Impact factor: 5.191