Cellular Infiltration and Cytokine Expression Correlate with Fistulizing State in Crohn's Disease

Abstract

The purpose of this study was to determine the degree of infiltration of different cell subpopulations (tissue dendritic macrophages, T-helper cells, cytotoxic T lymphocytes, monocytes, neutrophils, and B cells) and the expression of the cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-␣) in inflamed and noninflamed resected tissues from Crohn's disease (CD) and non-CD patients. Twenty-one resected fullthickness intestinal tissue specimens representing 13 subjects (8 CD and 5 non-CD patients) were included in this study. Sections of 20 m in thickness were cut and then stained using immunohistochemistry. The sections were analyzed using confocal laser scanning microscopy (CLSM). Patterns of staining for inflamed CD and noninflamed CD tissues versus non-CD tissues demonstrated significant differences in the macrophage and T-helper subpopulations. Surprisingly, the T-helper subset was decreased significantly in the inflamed CD sections compared to the noninflamed CD and non-CD sections. The staining patterns also suggested differences in the expression of both IL-12 and TNF-␣ between the groups, with cytokine overexpression directly relating to the fistulizing state in CD patients. Cytokine expression is upregulated in chronic CD patients; therefore, the degree of inflammation and tissue damage in CD is dependent on the expression of specific cytokines within the tissue. Differentiation of cell subpopulations may be important for establishing a direct relationship with each state of CD (inflammatory, stricturing, and fistulizing states).

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

“…( b ) Summary of observations on total CD4 + Th as well as Th1, Th2, Th17 and Treg subsets in tissue and blood of patients with sarcoidosis, Crohn's disease and CVID. 87, 88, 111, 112, 177, 178, 179, 180, 181, 182, 183, 184 …”

“…54,85 Upregulation of cytokines promoting Th1 differentiation have been reported in sarcoidosis: IL-2, IL-12, IL-15 and IL-18. 86 Th cell involvement in sarcoidosis is underpinned by the typical CD4 87,88,111,112,[177][178][179][180][181][182][183][184] T-cell lymphopenia in peripheral blood in combination with CD4 T-cell infiltrates at the site of inflammation, such as in bronchoalveolar lavage fluid. 87,88 Despite these signs of local T-cell hyperactivity, the typical diminished cutaneous response to tuberculin is suggestive of T-cell anergy in non-granulomatous tissue.…”

Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn’s Disease-Associated Adherent-Invasive Escherichia coli

“…They have increased survival ability within macrophages, where they induce continuous inflammatory cytokine secretion in vitro ( 2 – 4 ), possibly being a key event triggering inflammation and affecting CD chronicity ( 5 ). In addition, macrophages are found in greater numbers on inflamed tissue in CD patients ( 6 ). Some AIEC strains have been sequenced and well described and are therefore used as reference strains.…”

VEN-120, a Recombinant Human Lactoferrin, Promotes a Regulatory T Cell [Treg] Phenotype and Drives Resolution of Inflammation in Distinct Murine Models of Inflammatory Bowel Disease

“… 1–3 This immune dysregulation results in an overproduction of pro-inflammatory cytokines such as tumour necrosis factor [TNF] by monocytes, macrophages, and T cells, thereby allowing for persistence of a hyperactivated immune response. 4 , 5 CD4 + T cells are critical drivers of pathogenesis in IBD, whereby an increase in activation and populations of CD4 + and CD8 + T cells are observed in patients with IBD. 6 More recently, it has been appreciated that over-activation of Th1/Th17 T cell phenotypes drives much of the chronic pathology in IBD.…”