Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice

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Locachevic, Gisele Aparecida ; Tartari Pereira, Priscilla Aparecida ; Secatto, Adriana ; Fontanari, Caroline ; Galvao, Alyne Favero ; Borges Prado, Morgana Kelly ; Zoccal, Karina Furlani ; Petta, Tania ; Beraldo Moraes, Luiz Alberto ; Ramos, Simone Gusmao ; de Castro, Fabola Attie ; Sorgi, Carlos Arterio ; Faccioli, Lucia Helena

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2015, p. 11-pg., 2015-01-01.

Abstract

Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80(+)/CD80(+) and F4/80(+)/CD86(+) cells to the bronchoalveolar space, induced higher production of IFN-gamma, IL-6, MIP-1 alpha, MCP-1, and LTB4, reduced PGE(2) concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection. (AU)

• FAPESP's process: 09/07169-5 - Lipid mediators as regulators of immune response
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/04704-7 - Role of erythropoietin Histoplasma capsulatum infection
• Grantee: Gisele Aparecida Locachevic
• Support Opportunities: Scholarships in Brazil - Master