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


METHODS
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.
Griga
T
T
Department of Gastroenterology, University Hospital Bergmannsheil, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. thomas.griga@ruhr-uni-bochum.de
Hebler
U
U
Voigt
E
E
Tromm
A
A
May
B
B
D000328:Adult; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008222:Lymphokines / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015847:Interleukin-4