Association of Type 2 Cytokines with Hepatic Fibrosis in HumanSchistosoma mansoniInfection
Amélia Ribeiro de JesusAndréa MagalhãesDelfin Gonzalez MirandaRoberval Gonzalez MirandaMaria Ilma AraújoAdriana Almeida de JesusÂngela SilvaLuciana B. SantanaEdward J. PearceEdgar M. Carvalho
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ABSTRACT The objective of this study was to evaluate the role of cytokines in hepatic fibrosis in the prehepatosplenic and early hepatosplenic stages of schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94 patients. Immunological evaluation was performed by the measurement of secreted cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis factor alpha, and transforming growth factor β) in peripheral blood mononuclear cells (PBMC) stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic fibrosis compared to patients with degree I or II fibrosis. Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for 1 year following initial assessment and developed more serious fibrosis during this period. The data suggest a role for type 2 cytokines in hepatic fibrosis in human schistosomiasis mansoni.Keywords:
Hepatic fibrosis
Schistosoma
Questions Schistosomiasis (formerly Bilharzia) is a parasitic infectious disease provoked by Schistosoma mansoni. The disease is endemic in tropical and recently in temperate climate areas, such as Corsica. The WHO estimates the number of people affected by schistosomiasis > 240 million. Previously, we have shown that schistosomes influence the hepatic lipid metabolism. The present project aims to investigate the metabolic pathways by which S. mansoni eggs influence the hepatic lipid metabolism of the host.
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"Comparative Study of Schistosoma Mansoni Isolated from Patients with Hepatosplenic and Intestinal Clinical Forms of Schistosomiasis" published on Sep 1984 by The American Society of Tropical Medicine and Hygiene.
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A number of Erythrocebus patas monkeys have been experimentally infected only once, with Schistosoma mansoni local strain. The various parasitological, biological and immunological observations show that E. patas is a very adequate host to Schistosoma mansoni and that it develops an intestinal schistosomiasis parasitologically very close to human schistosomiasis. It is noted that in this case of single infection E. patas reactions are the same as the other species generally used in the experiments on S. mansoni.
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In some regions of the world, co-existence of schistosomiasis and hepatitis C (HCV) infection is common. Because the morbidity in human schistosomiasis is primarily due to host cell-mediated immune response, it was of interest to determine the effects on Schistosoma mansoni infection of an immune stimulator used in the standard treatment of HCV infection. Schistosoma mansoni-infected mice were treated with PEG-interferon-α-2a (PEG-IFN-α) by subcutaneous injection. Groups 1, 2, and 3 received 0.2 µg, 0.6 µg, and 1 µg PEG-IFN-α/wk, respectively, while group 4 received saline. The total worm burden was lower in all treated groups, with a maximal reduction of 35% after 9 wk of treatment with 1 µg PEG-IFN-α. Interferon treatment also increased the proportion of single worms over pairs. Ova counts in intestine and liver, as well as the number of liver granulomas, were greatly decreased at all time points for all treated groups. PEG-IFN-α also had inhibitory effects on the size of granulomas after 4 wk of treatment. The results suggest that PEG-IFN-α may be worth investigating for the treatment of human schistosomiasis when standard oral agents cannot be used, or when rapid inhibition of granuloma formation may be a priority.
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A case of cutaneous schistosomiasis with lesions on the trunk caused by eggs of Schistosoma mansoni is described. A brief review of the reported cases of cutaneous ectopic schistosomiasis by S. mansoni in made. The different forms of cutaneous lesions caused by schistosoma are considered.
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C57BL/6 mice infected with Schistosoma mansoni at day 0 and injected with cyclosporin A (CyA) either daily or from day -1 to day 3 were protected against schistosomiasis mansoni as indicated by a decrease in the number of worms recovered from the liver 45 days after infection. CyA treatment also protected rats and strains of mice with known immunity defects (nu/nu, P/N, CBA/N). Protection was evident against both primary and secondary infection in mice infected at day 0, reinfected at day 42, and treated daily with CyA either during the course of the experiment or only from day -1 to day 3, as indicated by the worm burden at day 67. In such an experiment of infection and reinfection, the immature worms were shown to be the target of CyA. Administration of the drug 27, 45, 62, or 100 days before infection confirmed the long-term protective effect of CyA. This drug did not evoke the killing of adult worms in vivo. These data confirm and define the curative and preventive effect of CyA against schistosomiasis mansoni.
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