Studies about the effects of the in vivo administration of Leukotriene B4 or Prostaglandin E2-loaded biodegradable microspheres on model of murine histoplasmosis / Estudos sobre os efeitos da administração in vivo de microesferas biodegradáveis contendo Leucotrieno B4 ou Prostaglandina E2 em modelo de histoplasmose murina

AUTOR(ES)

Roberto Nicolete

DATA DE PUBLICAÇÃO

2008

RESUMO

Leukotrienes and prostaglandins are arachidonic acid metabolites, which participate in the inflammatory response and modulate cytokines release in both adaptive and innate immune responses. However, some physicochemical characteristics of these mediators, such as poor solubility in water and chemical instability, make them difficult to administer in vivo. In this sudy, we developed a polymeric microparticulate system for the encapsulation of lipid mediators. Regarding the in vitro characterization of the microspheres, we determined their diameters, evaluated the in vitro release of the mediators and the microspheres uptake by peritoneal macrophages. To assess the preservation of the biological activities of these mediators, we conducted intravital microscopy studies and determined the effect of LTB4 and PGE2-loaded biodegradable microspheres on inflammatory mediators release by murine peritoneal macrophages and human endothelial cells. In mice infected by H. capsulatum, we investigated the effects of intranasal administration of the microspheres on pulmonary inflammatory response. In this context, we analyzed the inflammatory cells recruited to the bronchoalveolar space, the mice survival and the number of CFUs recovered from the lungs after the administrations. We also assessed the cytokines release by the lung cells after the treatment with microspheres during the course of the infection. In conclusion, our findings showed that biodegradable microspheres could preserve the biological activity of the encapsulated mediators indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.

ASSUNTO(S)

immunomodulation biodegradable microspheres lipid mediators imunomodulação mediadores lipídicos histoplasmose microesferas biodegradáveis histoplasmosis

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