The effect of statins as immune modulators during experimental Trypanosoma cruzi infection

• Grant number: 08/09851-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2009
• End date: March 31, 2010
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Fredy Roberto Salazar Gutierrez
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 07/53940-0 - The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases, AP.TEM

Abstract

In spite of the effectiveness in control of Chagas disease transmission reached through strategies targeting elimination of vector from housing, the disease is still a major menace to public health in Latin America. Current specific chemotherapy against Trypanossoma cruzi is unsatisfactory because of available drugs possess limited efficacy at the chronic stages of the diseases -which are the most prevalent- and because of the wide range of side effects. Therefore, it is necessary to seek for novel safer and more secure agents. Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, an enzyme responsible for the synthesis of cholesterol, mainly in the liver. Used in therapeutics of hypercholesterolemy, these medicaments are highly safe, and possess immune-modulatory effects that are pleiotropic and independent of their effect over cholesterol. Additionally, these substances have parasiticidal activity, specifically against T. cruzi, through indirect inhibition of ergosterol synthesis, required in the parasite's metabolism. Recent advances in pathophysiology of Chagas disease changed the insight from a perspective centered on auto-immunity as exclusive pathogenic mechanisms towards a point of view where pathogenesis of cardiomyopathy is determined by parasite persistence, in association with disequilibrium in immune response. Thus, therapeutic approaches regarding anti-parasitic treatment, along with modulation of immune response, could be highly benefic for the infected host. Therefore, statins are promissory in T. cruzi infection therapeutic arsenal, since they have microbicidal and immune-modulatory activities simultaneously. The objective of the present study is to test the therapeutic potential of statins in vivo in experimental T. cruzi infection. (AU)