Abstract
Objective:
To relate proinflammatory cytokines to leukocyte surface markers and adhesion molecules in the same paraffin-embedded biopsy specimen in inflammatory bowel disease (IBD) of varying activity.
Methods:
Biopsies of seven cases of Crohn's disease, seven patients with ulcerative colitis, one case of intestinal infection and six control subjects were studied. We performed in situ hybridization on sections of tissue using probes specific to interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF alpha). Leucocyte markers and adhesion molecules were investigated in subsequent slides of selected specimens by immunohistochemistry.
Results:
Cytokine mRNA was found in large numbers of cells throughout the inflamed intestine but also in some macroscopically unaffected tissue specimens. Transcripts were predominantly located within the lamina propria where immunohistochemistry of parallel sections revealed numerous macrophages and the presence of endothelial adhesion molecules. The expression of the different cytokines was closely related to each other and to histological but not to macroscopic (endoscopic) activity.
Conclusions:
The synthesis of IL-1beta IL-6 and TNF alpha mRNA is coordinately regulated. Cytokine production is located mostly in the lamina propria at sites that are rich in macrophages and show abundant staining of vascular adhesion molecules. This cascade of immune events is related to inflammatory cell infiltration in both Crohn's disease and ulcerative colitis.
MeSH terms
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Adult
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Aged
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Antigens, CD / analysis
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Antigens, CD / genetics
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Antigens, Differentiation, Myelomonocytic / analysis
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Antigens, Differentiation, Myelomonocytic / genetics
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Biopsy
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CD3 Complex / analysis
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CD3 Complex / genetics
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Cell Adhesion Molecules / analysis*
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Cell Adhesion Molecules / genetics
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Colitis, Ulcerative / metabolism*
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Colitis, Ulcerative / pathology
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Crohn Disease / metabolism*
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Crohn Disease / pathology
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Cytokines / analysis*
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Cytokines / genetics
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E-Selectin / analysis
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E-Selectin / genetics
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Female
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HLA-DR Antigens / analysis
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HLA-DR Antigens / genetics
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Humans
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Immunohistochemistry
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Inflammation Mediators / analysis
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Intercellular Adhesion Molecule-1 / analysis
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Intercellular Adhesion Molecule-1 / genetics
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Interleukin-1 / analysis
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Interleukin-1 / genetics
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Interleukin-6 / analysis
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Interleukin-6 / genetics
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology
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Leukocytes / pathology
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Lipopolysaccharide Receptors / analysis
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Lipopolysaccharide Receptors / genetics
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Lymphocyte Function-Associated Antigen-1 / analysis
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Lymphocyte Function-Associated Antigen-1 / genetics
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Macrophages / pathology
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Male
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Middle Aged
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RNA, Messenger / analysis
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / genetics
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD3 Complex
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CD68 antigen, human
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Cell Adhesion Molecules
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Cytokines
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E-Selectin
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HLA-DR Antigens
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Inflammation Mediators
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Interleukin-1
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Interleukin-6
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Lipopolysaccharide Receptors
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Lymphocyte Function-Associated Antigen-1
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1