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Flavonoid treatment in patients with healed venous ulcer: flow cytometry analysis suggests increased CD11b expression on neutrophil granulocytes in the circulation

Department of Vascular Diseases, Malmö University Hospital, Malmö, Sweden, gudmundurdanielsson{at}yahoo.com

Lars Norgren

Department of Vascular Diseases, Malmö University Hospital, Malmö, Sweden

Lennart Truedsson

Department of Clinical Microbiology and Immunology, Lund University Hospital, Sweden

Annica Andreasson

Department of Clinical Microbiology and Immunology, Lund University Hospital, Sweden

Peter Danielsson

Department of Vascular Diseases, Malmö University Hospital, Malmö, Sweden

Anna Nilsson

Department of Vascular Diseases, Malmö University Hospital, Malmö, Sweden

Paul Swartbol

Division of Surgery, University Hospital Utrecht, Netherlands

The objective was to determine the activation of white blood cells (WBCs) and endothelial cells in patients with healed venous ulcer and the influence of the standing position and of treatment with flavonoids. Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days. Blood samples were taken from arm and dorsal foot veins before and after standing for 30 minutes. Blood sampling was performed before treatment, after three days, one month and three months. The activation of WBCs was determined by measuring adhesion molecule CD11b and CD18 expression on the surface of granulocytes and monocytes. In addition, interleukin 6 (IL-6), IL-8, soluble E-selectin (sE-selectin), sL-selectin and sICAM-1 levels in serum were quantified. The results showed that standing did not influence any of the measured parameters significantly. Expression of CD11b adhesion molecules on granulocytes was significantly up-regulated (p = 0.044) after treatment with flavonoids for one month, but this increase was not significant (p = 0.056) two months after the treatment period compared with the baseline level. The expression of CD18 remained unchanged. Baseline expression of CD11b or CD18 on monocytes did not change significantly during the study period. Neither was any significant change observed in the levels of IL-6, IL- 8 or the soluble adhesion molecules. It was concluded that flavonoid treatment for 30 days increased the expression of CD11b adhesion molecules on circulating granulocytes. No general effect on the inflammatory process could be observed as assessed by levels of cytokines and soluble adhesion molecules. Possible explanations for these findings could be that a decreased number of primed granulocytes leave the circulation due to a changed WBC/endothelial cell interaction or that flavonoids have a direct effect on granulocytes. Further studies are needed to clarify the mode of action of flavonoids in chronic venous disease.

Key Words: adhesion molecule • chronic venous disease • endothelial factors • white blood cell activation

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