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Targeting IL-27 and/or IL-10 in Experimental Murine Visceral Leishmaniasis

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  • 1 Division of Infectious Diseases, Department of Medicine, Well Cornell Medical College, New York, New York

ABSTRACT

Interleukin-10 (IL-10) and interleukin-27 (IL-27) both exert counterregulatory immunodeactivation in visceral Leishmania donovani infection. We studied experimental L. donovani infection in the livers of IL-10−/− and IL-27Rα−/− mice and observed that in IL-27Rα−/−, but not IL-10−/− mice, interferon-gamma (IFN-γ) and tumor necrosis factor (TNF) were required for heightened granulomatous inflammation and accelerated control of intracellular parasite replication. This difference in mechanism, along with residual IL-10 activity in IL-27Rα−/− mice, suggested targeting IL-27 in addition to IL-10 in a macrophage-activating, anti-counterregulatory cytokine treatment strategy. In C57BL/6 wild-type mice with established liver infection, a single injection of anti–IL-27 p28 or anti–IL-10R monoclonal antibody enhanced granuloma assembly, enabled macrophage activation, and induced comparable parasite killing (49–56%). However, anti–IL-27 p28 plus anti–IL-10R combination treatment did not increase leishmanicidal effects. These results suggest that IL-27 and IL-10 may operate in a linked deactivating mechanism and that in this intracellular infection, either IL-27 or IL-10 is a suitable immunotherapeutic target.

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Author Notes

Address correspondence to Henry W. Murray, Division of Infectious Diseases, Department of Medicine, Well Cornell Medical College, 1300 York Ave., New York, 1. E-mail: hwmurray@med.cornell.edu

Financial support: This study was supported by NIH grant 5R01AI083219.

Author’s address: Henry W. Murray, Division of Infectious Diseases, Department of Medicine, Well Cornell Medical College, New York, NY, E-mail: hwmurray@med.cornell.edu.

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