Chapter 2 : Cytokines and Chemokines in Granulomatous Inflammation

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This chapter summarizes the current understanding of the role of molecular mediators in granuloma formation as derived from studies of human disease and animal models. In the broadest definition, cytokines include lipid, nucleotide, and protein mediators, since all of these types of molecules have effects on immune cell function, but the discussion in the chapter focuses only on the protein mediators known as interferons (IFNs), interleukins (ILs), tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), and growth factors (GFs). The roles that some of the major groups of cytokines play in granulomatous responses are discussed. Once the granuloma is established, chemokines could also help to sustain the lesion and regulate resolution phase sequela such as neovascularization and fibrosis. It is likely that chemokines participate extensively in the granulomatous response. The chapter summarizes some of the mounting evidence that appears to support this hypothesis. Other reported chemokine-inhibiting cytokines include Th2-related chemokines IL-4 and IL-13, but these cytokines have also been demonstrated to promote the production of some CC chemokines, such as CCL2 (MCP-1) in endothelial cells and granuloma fibroblasts. Evidence provided by many investigators over the past two decades provides strong support for the dynamic participation of cytokines and chemokines in granuloma formation.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 1

Cytokine grouping by utilized transduction pathway.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 2

Classification of hypersensitivitytype granulomas by cytokine patterns.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 3

Chemokine groups and their receptors. Old nomenclature is shown after the dashes.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 4

Characterization of antigen-bead pulmonary granuloma models. (A) Histologic appearance of developing type-1 (mycobacterial PPD), type-2 (schistosomal SEA), and antigen- free control (CON) bead granulomas; (B) cellular composition; (C) granuloma culture cytokines; and (D) draining lymph node culture cytokine production during type-1 and type-2 Ag-bead granuloma formation.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 5

Pattern and temporalexpression of chemokines during type-1 (mycobacterial PPD) antigen-bead granuloma formation.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 6

Pattern and temporalexpression of chemokines during type-2 (schistosomal SEA) antigen-bead granuloma formation.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 7

Pattern and temporal expression of chemokine receptor mRNA in whole lungs with developing type-1 (mycobacterial PPD) and type-2 (schistosomal SEA) antigen-bead granulomas. Bars are arbitrary units derived from quantitative mRNA analysis.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Figure 8

Effect of antichemokine antibody treatments on sizes of type-1 (mycobacterial PPD) and type-2 (schistosomal SEA) antigen-bead granulomas. Bars are mean granuloma cross-sectional area measured on day 4 of development.

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Table 1

Chemokines reported in human granulomatous conditions

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2
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Table 2

Chemokine groups defined during experimental type-1 (PPD) and type-2 (SEA) antigen-bead hypersensitivity granuloma formation

Citation: Chensue S, Kunkel S. 2003. Cytokines and Chemokines in Granulomatous Inflammation, p 29-64. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch2

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