Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi Carla Domingues Santos * , Mı ´riam Paula Alonso Toldo, Fabrı ´cia Helena Santello, Marina Del Vecchio Filipin, Va ˆnia Braza ˜o, Jose ´ Clo ´vis do Prado Ju ´nior . Laborato ´rio de Parasitologia, Departamento de Ana ´lises Clı ´nicas, Toxicolo ´gicas e Bromatolo ´gicas, Faculdade de Cie ˆncias Farmace ˆuticas de Ribeira ˜o Preto (FCFRP-USP), Universidade de Sa ˜o Paulo, Avenida do Cafe ´ s/n, 14040-903 Ribeira ˜o Preto, SP, Brazil Received 2 August 2007; received in revised form 20 January 2008; accepted 24 January 2008 Abstract Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In a previous study, we reported that administration of DHEA significantly decreased the numbers of blood parasites in Trypanosoma cruzi experimental infection. The present study was undertaken to determine the effectiveness of DHEA in reducing the severity of acute phase T. cruzi infection of male and female Wistar rats. Animals were treated subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and interferon-gamma (IFN-g) were determined in the sera of uninfected and infected animals. DHEA treatment augments NO production for both sexes after in vitro LPS treatment for uninfected animals. Infection triggered enhanced NO levels although not significant. IL-2 and IFN-g were detectable in higher concentrations in treated and infected rats of both genders when compared to untreated controls. These data suggest that DHEA may have a potent immunoregulatory function that can affect the course of T. cruzi infection. # 2008 Elsevier B.V. All rights reserved. Keywords: Trypanosoma cruzi; Dehydroepiandrosterone; Nitric oxide; Interleukin-2; Interferon-gamma 1. Introduction Chagas’ disease or American trypanosomiasis affects up to 20 million people in Central and South America and is caused by the blood-borne protozoan Trypanosoma cruzi, an obligate intracellular parasite that causes chronic infections in humans and a large number of other mammalian species (WHO, 2002). Infection results in the development of type 1 and type 2 patterns of cytokine response during acute and chronic phases of infection. For protection, the host builds a strong Th1 response whereas the Th2 response increases susceptibility (Del Prete and Romagnani, 1994). One of the cytokines involved during the early infection of T. cruzi infection is the production of the type 1 cytokine, interferon-gamma (IFN-g)(Reed, 1988; Nabors and Tarleton, 1991), while absence of IFN-g enhances parasitaemia and increases mortality in T. cruzi-infected mice (Torrico et al., 1991; Petray et al., 1993). In turn, IFN-g and TNF-a stimulate phagocytic cells to destroy internalized parasites, mainly through nitric oxide (NO) generation (Muno ˜z Ferna ´ndez et al., 1992) resulting in a raise of reactive intermediates from oxygen (Cardoni et al., 1997) and nitrogen (R = 7). Nitric oxide or nitrogen-derived metabolites have been www.elsevier.com/locate/vetpar Available online at www.sciencedirect.com Veterinary Parasitology 153 (2008) 238–243 * Corresponding author. Tel.: +55 16 602 4153; fax: +55 16 602 4163. E-mail address: carladom@fcfrp.usp.br (C.D. Santos). 0304-4017/$ – see front matter # 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.vetpar.2008.01.039