Down-regulation of interleukin-12, interleukin-12R expression/activity mediates the switch from Th1 to Th2 granuloma response during murine Schistosomiasis mansoni.

Abstract:

: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-12Rbeta2 and interferon (IFN)-gamma 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)-alpha and IFNgamma, whereas lymphocyte IL-12 responsiveness was boosted only by TNF-alpha. 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-gamma and IL-12Rbeta2, 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.

journal_name

Scand J Immunol

authors

Todt JC,Whitfield JR,Ivard SR,Boros DL

doi

10.1046/j.1365-3083.2000.00785.x

keywords:

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

385-92

issue

4

eissn

0300-9475

issn

1365-3083

pii

sji785

journal_volume

52

pub_type

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