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Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks.

S W Chensue, K Warmington, J H Ruth, N Lukacs and S L Kunkel
J Immunol October 1, 1997, 159 (7) 3565-3573;
S W Chensue
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K Warmington
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J H Ruth
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N Lukacs
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S L Kunkel
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Abstract

Type 1 (IFN-gamma/TNF-dominant) and 2 (IL-4/IL-5-dominant) granulomatous inflammation were analyzed in mice with knockout of IFN-gamma or IL-4 genes. Lung granulomas were elicited by beads coated with purified protein derivative (PPD) of Mycobacteria bovis or soluble Schistosoma mansoni egg Ags. Parameters included granuloma size, composition, and macrophage function; white blood cell differentials; lymph node cytokine profiles; and cytokine/chemokine mRNA expression by lungs. Type 1 (PPD) and 2 (soluble Schistosoma mansoni egg Ags) responses showed characteristic cytokine and chemokine profiles in control mice. IFN-gamma knockout converted the PPD response to a type 2-like pattern with eosinophil infiltration and decreased TNF and RANTES, but increased IL-4, IL-5, IL-10, IL-13, monocyte chemoattractant protein-3 (MCP-3), and eotaxin expression. IL-4 knockout exacerbated type 1 inflammation with increased IL-2/IFN-gamma production by lymph nodes and IL-1 production by granuloma macrophages, but unexpectedly, IFN-gamma transcripts were reduced in lungs. Regarding the type 2 response, IL-4 was needed for maximal blood eosinophilia, but surprisingly, its absence had a minimal effect on type 2 granuloma size and composition despite regional reductions of IL-5 and IL-10 as well as local reductions of TNF-alpha, MCP-1, MCP-3, and eotaxin. Thus, the type 2 granuloma was not converted to a type 1 composition with IL-4 knockout, but showed persistent expression of IL-13 and some degree of IL-5 and MCP-3, suggesting that these cytokines could potentially support a compensatory type 2 response. IFN-gamma knockout did not augment type 2 granuloma size or Th2 cytokines in lymph nodes and unexpectedly reduced IL-4 transcripts in lungs. This study offers important implications regarding inflammation and its relationship to local and regional cytokine expression.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 159, Issue 7
1 Oct 1997
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Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks.
S W Chensue, K Warmington, J H Ruth, N Lukacs, S L Kunkel
The Journal of Immunology October 1, 1997, 159 (7) 3565-3573;

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Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks.
S W Chensue, K Warmington, J H Ruth, N Lukacs, S L Kunkel
The Journal of Immunology October 1, 1997, 159 (7) 3565-3573;
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Print ISSN 0022-1767        Online ISSN 1550-6606