Avaliação dos efeitos do ácido caurenoico e do partenolido sobre a produção de citocinas e óxido nítrico em células de camundongos C57Bl/6 após indução da EAE

Abstract

Multiple sclerosis (MS) is an autoimmune disease, chronic, progressive, inflammatory and demyelinating disease of the central nervous system (CNS) that affects 2.5 million people worldwide. The experimental autoimmune encephalomyelitis (EAE) is the most accepted model for studying the pathogenesis of MS due to its clinical and histopathologic similarity to this disease. Both have pathophysiological processes mediated by Th1 and Th17 cells, with production of pro-inflammatory cytokines such as interferon-gamma (IFN-), Tumor Necrosis Factor-alpha (TNF-α) and interleukin 17 (IL-17) and mediated nitric oxide (NO), mainly produced by macrophages. Currently used medications for MS act on some of these inflammatory mediators, but due to the high cost and adverse effects displayed becomes necessary to search for new substances which are capable of modulating the production of these inflammatory mediators. Thus, in the present study investigated the in vitro effect immunomodulatory of the kaurenoic acid and parthenolide on the production of NO, TNF-α, IFN-, IL-17 and Interleukin 6 (IL-6) in splenocyte cultures of mice induced with EAE. For this, EAE was induced in female C57Bl/6 with MOG35-55 and animals were euthanized on the 22th day post induction for obtaining splenocytes. These cells restimulated with MOG35-55 and lipopolysaccharide (LPS) were given the substances tested at three different concentrations (25, 50 and 100 µM for kaurenoic acid and 1, 5 and 20 µM for the parthenolide). The kaurenoic acid reduced the levels of NO, TNF-α, IFN-, IL-6 and IL-17 at the two highest concentrations tested. Parthenolide was able decrease the production of IL-6 in all tested concentrations, although the NO and IL-17, was only decreased by the two highest concentration and TNF-α, IFN was decreased only the highest concentration analyzed. The results obtained in this study suggest that kaurenoic acid and parthenolide may modulate the production of inflammatory mediators, demonstrate the great potential of these substances as prototypes for the development of new approaches in EAE, an animal model of MS.