Interleukin-10 (IL-10) in experimental visceral leishmaniasis and IL-10 receptor blockade as immunotherapy Academic Article Article uri icon

Overview

MeSH Major

  • Amphotericin B
  • Antiprotozoal Agents
  • Leishmaniasis, Visceral

abstract

  • Interleukin-10 (IL-10) is thought to promote intracellular infection, including human visceral leishmaniasis, by disabling Th1 cell-type responses and/or deactivating parasitized tissue macrophages. To develop a rationale for IL-10 inhibition as treatment in visceral infection, Th1 cytokine-driven responses were characterized in Leishmania donovani-infected BALB/c mice in which IL-10 was absent or overexpressed or its receptor (IL-10R) was blockaded. IL-10 knockout and normal mice treated prophylactically with anti-IL-10R demonstrated accelerated granuloma assembly and rapid parasite killing without untoward tissue inflammation; IL-12 and gamma interferon mRNA expression, inducible nitric oxide synthase reactivity, and responsiveness to antimony chemotherapy were also enhanced in knockout mice. In IL-10 transgenic mice, parasite replication was unrestrained, and except for antimony responsiveness, measured Th1 cell-dependent events were all initially impaired. Despite subsequent granuloma assembly, high-level infection persisted, and antimony-treated transgenic mice also relapsed. In normal mice with established infection, anti-IL-10R treatment was remarkably active, inducing near-cure by itself and synergism with antimony. IL-10's deactivating effects regulate outcome in experimental visceral leishmaniasis, and IL-10R blockade represents a potential immuno- and/or immunochemotherapeutic approach in this infection.

publication date

  • November 2002

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1128/IAI.70.11.6284-6293.2002

PubMed ID

  • 12379707

Additional Document Info

start page

  • 6284

end page

  • 93

volume

  • 70

number

  • 11