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- Title
Determinants of Response to Interleukin-10 Receptor Blockade Immunotherapy in Experimental Visceral Leishmaniasis.
- Authors
Murray, Henry W.; Moreira, Andre L.; Lu, Cristina M.; DeVecchio, Jennifer L.; Matsuhashi, Maki; Ma, Xiaojing; Heinzel, Frederick P.
- Abstract
In established Leishmania donovani visceral infection in normal mice, anti-interleukin (IL)-10 receptor (IL10R) monoclonal antibody (MAb) treatment induced intracellular parasite killing within liver macrophages. IL-10R blockade maintained IL-12 protein 40, markedly increased interferon (IFN)-γ serum levels, and enhanced tissue inducible nitric oxide synthase (iNOS) expression and granuloma assembly. Optimal MAb-induced killing, including synergism with antimony chemotherapy, required endogenous IL-12 and/or IFN-γ and at least one IFN-γ-regulated macrophage mechanism—iNOS or phagocyte oxidase. However, in IFN-γ knockout mice, anti-IL-10R also induced both granuloma formation and leishmani-static activity. As judged by IL-10R blockade, endogenous IL-10 primarily regulates killing in L. donovani infection by suppressing production of and responses to the Thl cell-type cytokines, IL-12, and IFN-γ. However, because anti-IL-10R also released IFN-γ-independent effects, IL-10 appears to act more broadly and suppresses multiple antileishmanial mechanisms.
- Subjects
LEISHMANIASIS; INTERLEUKIN-10; IMMUNOTHERAPY
- Publication
Journal of Infectious Diseases, 2003, Vol 188, Issue 3, p458
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/376510