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Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis
Authors:Wheverton C. Nascimento  Roeckson P. Silva  Erica S. Fernandes  Maria C. Silva  Gabriela C. Holanda  Patrícia A. Santos  Mônica P. Albuquerque  Vlaudia A. Costa  Nicodemos T. Pontes-Filho  Valdênia O. Souza
Affiliation:1. Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, 50.670-901, Pernambuco, Brazil
2. Center of Research Aggeu Magalh?es (CPqAM), Oswaldo Cruz Foundation (Fiocruz), 50.670-420, Pernambuco, Brazil
3. Department of Tropical Medicine, Federal University of Pernambuco, 50.670-901, Pernambuco, Brazil
4. Department of Pathology, Federal University of Pernambuco, 50.670-901, Pernambuco, Brazil
5. Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50.670-901, Pernambuco, Brazil
Abstract:
Adult worm extract from Ascaris suum (Asc) has immunosuppressive activity and elicits Th2/IL-4/IL-10 response. This study evaluated the prophylactic and therapeutic effect of Asc in a murine model of concanavalin A (ConA)-induced autoimmune hepatitis (AIH). BALB/c mice received ConA, iv, (20 mg/kg), and three groups of animals were formed: (1) AIH, received only ConA; (2) AIH + Asc prophylactic, treated with Asc (1 mg/ml), ip, 30 min before of the AIH; and (3) AIH + Asc therapeutic, treated with Asc 2 h after the AIH. Plasma transaminase and immunoglobulins (measured at 8 and 24 h and 7 days after treatment) and cytokine production (IL-4, IL-10, IL-13, and IFN-γ) by splenocytes upon ConA and Asc stimulus were compared. The livers were weighed and examined histologically. In the AIH group, there was an increase in liver weight, transaminase levels, and total immunoglobulins. These parameters were reduced by 8–24 h and 7 days in the prophylactic group, but in the therapeutic group, only on day 7. The survival rate of mice in the AIH group was 38.5 %, compared to 67 % in the therapeutic Asc group. The survival rate of the animals with AIH that were prophylactically treated with Asc was 100 %. A decrease of cellular infiltration and high levels of IL-4, IL-10, and IL-13 were induced by Asc. An increase of liver fibrosis was also observed, but with less intensity with prophylactic treatment. Thus, the Ascaris components have an inhibitory effect on AIH, with an intense Th2 immune response.
Keywords:
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