Influência do tratamento com antifúngico e antiinflamatório na resposta granulomatosa da paracoccidiodomicose experimental murino: pesquisa de anticorpos e citocinas

Abstract

The etiologic agent of paracoccidioidomycosis (PCM) is the thermo-dimorphic fungus Paracoccidioides spp. (Pb). PCM is a systemic mycosis with the highest prevalence in Brazil. It mainly affects male individuals who may be linked to the exercise of rural activities. To understand the interaction of this fungus with the host, studies used the murine experimental model and it was possible to classify several strains of mice infected with Pb and the mechanisms that are involved in the granulomatous inflammatory immune response. It is worth mentioning that the presence of granulomas characterizes this ringworm. The expression of cytokines and the presence of antibodies of various isotypes at the sites of granulomatous lesions is still poorly studied. Therefore, this study aimed to verify the influence of treatment through the stereological study, the search for specific antibodies of the IgM, IgG, IgG1a, IgG2a, IgG2b, cytokines IL17, KC (IL8) and GM-CSF in paracoccidioidomycotic granulomas present in the organs of mice infected with P. brasiliensis and treated and not treated with Itraconazole (antifungal) and Celecoxib (anti- inflammatory). For this, it was also considered that the treatments available are limited nowadays and the study of new alternatives can help the understanding of the defense mechanisms and the acute or chronic inflammatory processes acting in the PCM. Therefore, Swiss mice infected with the virulent strain Pb18 of P. brasiliensis were used. The necropsy was performed and the spleen, omentum, liver and lungs were collected and histological analyzes were performed to check the architecture, cellularity, presence of P. brasiliensis yeasts in granulomatous lesions and the morphological remodeling by the stereological method. The results showed that the animals that received combined treatments had smaller histological lesions and presented better histological patterns, weight, survival, hypersensitivity, production of antibodies, cytokines and fewer viable fungi. In addition, the results of immunohistochemistry the data show that there was a strong marking for the presence of IgM, IgG, IL-17 and GM-CSF in different stages of the infection. From these results, it can be concluded that the combined treatment showed satisfactory results both in the early and late stages of this disease. Suggesting that this therapeutic combination reduces the intense inflammatory response in patients, it could be used as a possible new treatment strategy.