BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.

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PubMedDate not supplied

Interleukin-4 inhibits the increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF), a potent angiogenic, permeability-enhancing cytokine plays an important role in tissue repair and chronic inflammatory disorders. Peripheral blood mononuclear cells (PBMCs) and the inflamed mucosa have been demonstrated to be main sources of the recently described circulating VEGF in patients with inflammatory bowel disease (IBD). There is no current information about the influence of immunoregulatory cytokines on VEGF in IBD. The present study examines the effect of interleukin-4 on the increased VEGF production of PBMCs in patients with IBD. METHODOLOGY: Unstimulated PBMCs from 17 patients with Crohn's disease, 16 patients with ulcerative colitis and 8 healthy controls were cultured with or without IL-4. VEGF production was measured in the supernatant using an enzyme-linked immunosorbent assay. RESULTS: IL-4 led to a significant reduction of the VEGF production by PBMCs of both active Crohn's disease patients (471.7 +/- 377.5 pg/mL vs. 208.2 +/- 123.2 pg/mL, P = 0.018, n = 7) and active ulcerative colitis patients (177.1 +/- 79.4 pg/mL vs. 87.4 +/- 77.2 pg/mL, P = 0.008, n = 9). IL-4 inhibited significantly the VEGF production by PBMCs of patients with inactive Crohn's disease (179.2 +/- 133.9 pg/mL vs. 87.7 +/- 56.6 pg/mL, P = 0.005, n = 10). There was no significant difference of VEGF release by PBMCs cultured with IL-4 in patients with active Crohn's disease or active ulcerative colitis compared with PBMCs cultured without IL-4 in patients with inactive disease and healthy controls (112.6 +/- 41.9 pg/mL, n = 8). CONCLUSIONS: IL-4 has been shown to reduce the increased VEGF production of PBMCs in patients with IBD to normal levels. The known defective immunosuppressive effect of IL-4 in IBD may contribute to the pathogenic cascade leading to inflammation by VEGF mediated mechanisms.

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