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Down‐Regulation of Interleukin‐12, Interleukin‐12R Expression/Activity Mediates the Switch from Th1 to Th2 Granuloma Response during Murine Schistosomiasis Mansoni
Author(s) -
Todt J. C.,
Whitfield J. R.,
Ivard S. R.,
Boros D. L.
Publication year - 2000
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2000.00785.x
Subject(s) - granuloma , immunology , interleukin , biology , tumor necrosis factor alpha , interleukin 4 , schistosoma mansoni , interleukin 12 , inflammation , cytokine , interferon , interferon gamma , interleukin 2 , schistosomiasis , macrophage , in vitro , cytotoxic t cell , helminths , biochemistry
In murine schistosomiasis mansoni the worm egg‐induced granulomatous inflammation is bi‐phasic: an initial Th1 type is subsequently switched to a Th2 type response. Analysis of the cellular, molecular base of the Th1‐associated response (5–6 weeks post infection) revealed mRNA messages for interleukin (IL)‐12 p40, IL‐12Rβ2 and interferon (IFN)‐γ in the granulomatous livers. When the Th2 type granulomas matured (8 weeks post infection) message expression weakened or became extinct. Macrophages of the Th1 type granulomas produced maximal amounts of IL‐12, but production diminished in the mature granulomas. A similar pattern of IL‐12 responsiveness of granuloma lymphocytes was observed. In vitro IL‐12 production by Th1 type granuloma macrophages was enhanced by tumour necrosis factor (TNF)‐α and IFNγ, whereas lymphocyte IL‐12 responsiveness was boosted only by TNF‐α. Both systems were down‐regulated by IL‐4 and IL‐10 cytokines. Treatment of mice with anti‐IL‐10 monoclonal antibodies (MoAb) between 6 and 7 weeks of the infection enhanced mRNA expression for IFN‐γ and IL‐12Rβ2, but not for IL‐12 p40. It is concluded that IL‐12 and IL‐12R expression and function regulate the Th1 phase of the liver granulomatous response. This phase is cross‐regulated by type‐2 cytokines especially IL‐10.