EFEITO DO PRAZIQUANTEL NA RESPOSTA IMUNE DE CAMUNDONGOS INFECTADOS POR Schistosoma mansoni DURANTE 60 E 90 DIAS

Abstract

Schistosomiasis mansoni is caused by Schistosoma mansoni and chemotherapy has been carried out with praziquantel (PZQ) for more than 40 years. Although the World Health Organization prescribes the use of praziquantel, the drug continues to be researched to better understand its mode of action on the parasite and its effects on the host immune response and to fill gaps. The aim of this thesis is to compile previously described mechanisms of action of PZQ in Schistosoma and new therapeutic perspectives, as well as to investigate the effects on the immune response following treatment with the drug in the acute and chronic phases of the disease. In Chapter I, we conducted a narrative literature review in which we addressed the previously described mechanisms of action, reiterating that there is still no consolidated rationale for the lower efficacy of PZQ in immature stages of the worm. In addition, we present a compilation of new therapeutic perspectives regarding the use of PZQ as an adjuvant in the production of vaccines to enhance the immune response. Chapter II was prepared from in vitro and in vivo experiments related to PZQ and S. mansoni. In vitro experiments were performed with adult worms exposed to different concentrations of PZQ (0.1, 1 and 10 μg/mL) to evaluate their mobility and mortality. All concentrations analyzed showed an effect on worm mortality. However, the survival time of the worms in the experiment increased with decreasing concentration. To obtain in vivo data, male mice were experimentally infected with S. mansoni cercariae and treated with PZQ for seven consecutive days (from day 45 to 51 post-infection). The euthanasia of the animals was divided into two intervals of disease progression: part of the animals at 60 days of infection (acute phase) and the rest at 90 days (chronic phase) to perform parasitologic, histopathologic and immunologic analyzes. For both phases of the disease, PZQ was found to reduce the number of eggs in the liver and feces as well as the number of granulomas in the liver. In the intestine, a reduction in granulomas was only observed in the chronic phase. This reduction in the parasite load and the presence of granulomas was also accompanied by a reduction in the cellular infiltrate, tissue damage in the liver and intestine as well as a decrease in eosinophils and an increase in lymphocytes. Regarding the response profile generated during infection, it was observed that PZQ affected the production of cytokines from the Th1, Th2 and Treg profiles. For both periods analyzed (acute and chronic), a decrease in the concentrations of TNF-α, IL-6 and IL-10 was observed. From this we can conclude that, in addition to its recognized antiparasitic role, the drug also acts as an anti-inflammatory agent in both phases, modulating the immune response and possibly associated with a reduction in tissue pathology.