Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis Academic Article uri icon

Overview

MeSH Major

  • Antimony Sodium Gluconate
  • Body Fluids
  • Gluconates
  • Interferon-gamma
  • Interleukin-2
  • Intracellular Fluid
  • Leishmaniasis, Visceral
  • T-Lymphocytes

abstract

  • Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-gamma or interleukin 2 alone. The absence of this T cell- and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.

publication date

  • January 1989

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC303815

PubMed ID

  • 2539396

Additional Document Info

start page

  • 1253

end page

  • 7

volume

  • 83

number

  • 4