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Henry W. Murray, Moreira Andre L., Cristina M. Lu, Jennifer L. DeVecchio, Maki Matsuhashi, Xiaojing Ma, Frederick P. Heinzel, Determinants of Response to Interleukin-10 Receptor Blockade Immunotherapy in Experimental Visceral Leishmaniasis, The Journal of Infectious Diseases, Volume 188, Issue 3, 1 August 2003, Pages 458–464, https://doi.org/10.1086/376510
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Abstract
In established Leishmania donovani visceral infection in normal mice, anti-interleukin (IL)-10 receptor (IL-10R) 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 leishmanistatic 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 Th1 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.
- cytokine
- antimony
- chemotherapy regimen
- monoclonal antibodies
- cells
- granuloma
- immunotherapy
- interferons
- interleukin-10
- interleukin-12
- interleukins
- leishmania donovani
- leishmaniasis, visceral
- macrophages
- mice, knockout
- nitric oxide synthase
- parasites
- phagocytes
- infections
- liver
- mice
- human leukocyte interferon
- oxidase
- interleukin-10 receptor
- killing