Endogenous interleukin-18 is involved in immunity to Leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate

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Abstract

Immunity to Leishmania donovani is associated with an interleukin (IL)-12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL-18, which can modulate both interferon (IFN)-gamma and IL-4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL-18-deficient and wild type mice. IL-18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL-18-deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN-gamma production as well as lower serum IL-12 and IFN-gamma levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL-12 and IFN-gamma levels, and IFN-gamma production by ConA stimulated splenocytes of IL-18-deficient mice, to levels equivalent to similarly treated wild type mice.

LanguageEnglish
Pages348-354
Number of pages7
JournalImmunology
Volume119
Issue number3
Early online date26 Jul 2006
DOIs
Publication statusPublished - Nov 2006

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Antimony Sodium Gluconate
Leishmania donovani
Interleukin-18
Interferon-gamma
Immunity
Interleukin-12
Concanavalin A
Infection
Therapeutics
Wild Animals
Serum
Interleukin-4
Pharmaceutical Preparations
Parasites
Spleen
Bone Marrow
Drug Therapy
Liver

Keywords

  • animals
  • antibodies, protozoan
  • antimony sodium gluconate
  • antiprotozoal agents
  • cells, cultured
  • disease susceptibility
  • immunoglobulin G
  • interferon-gamma
  • interleukin-12
  • interleukin-18
  • leishmania donovani
  • leishmaniasis, visceral
  • mice
  • mice, Inbred BALB C
  • spleen
  • Th1 cells
  • treatment outcome

Cite this

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title = "Endogenous interleukin-18 is involved in immunity to Leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate",
abstract = "Immunity to Leishmania donovani is associated with an interleukin (IL)-12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL-18, which can modulate both interferon (IFN)-gamma and IL-4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL-18-deficient and wild type mice. IL-18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL-18-deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN-gamma production as well as lower serum IL-12 and IFN-gamma levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL-12 and IFN-gamma levels, and IFN-gamma production by ConA stimulated splenocytes of IL-18-deficient mice, to levels equivalent to similarly treated wild type mice.",
keywords = "animals, antibodies, protozoan, antimony sodium gluconate, antiprotozoal agents, cells, cultured, disease susceptibility, immunoglobulin G, interferon-gamma, interleukin-12, interleukin-18, leishmania donovani, leishmaniasis, visceral, mice, mice, Inbred BALB C, spleen, Th1 cells, treatment outcome",
author = "Mullen, {Alexander B.} and Lawrence, {Catherine E.} and Emma McFarlane and Xiao-Quing Wei and Carter, {Katharine C.}",
year = "2006",
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T1 - Endogenous interleukin-18 is involved in immunity to Leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate

AU - Mullen, Alexander B.

AU - Lawrence, Catherine E.

AU - McFarlane, Emma

AU - Wei, Xiao-Quing

AU - Carter, Katharine C.

PY - 2006/11

Y1 - 2006/11

N2 - Immunity to Leishmania donovani is associated with an interleukin (IL)-12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL-18, which can modulate both interferon (IFN)-gamma and IL-4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL-18-deficient and wild type mice. IL-18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL-18-deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN-gamma production as well as lower serum IL-12 and IFN-gamma levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL-12 and IFN-gamma levels, and IFN-gamma production by ConA stimulated splenocytes of IL-18-deficient mice, to levels equivalent to similarly treated wild type mice.

AB - Immunity to Leishmania donovani is associated with an interleukin (IL)-12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL-18, which can modulate both interferon (IFN)-gamma and IL-4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL-18-deficient and wild type mice. IL-18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL-18-deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN-gamma production as well as lower serum IL-12 and IFN-gamma levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL-12 and IFN-gamma levels, and IFN-gamma production by ConA stimulated splenocytes of IL-18-deficient mice, to levels equivalent to similarly treated wild type mice.

KW - animals

KW - antibodies, protozoan

KW - antimony sodium gluconate

KW - antiprotozoal agents

KW - cells, cultured

KW - disease susceptibility

KW - immunoglobulin G

KW - interferon-gamma

KW - interleukin-12

KW - interleukin-18

KW - leishmania donovani

KW - leishmaniasis, visceral

KW - mice

KW - mice, Inbred BALB C

KW - spleen

KW - Th1 cells

KW - treatment outcome

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VL - 119

SP - 348

EP - 354

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