Role of Leukocyte Activation in Patients with Venous Stasis Ulcers

• Published in: The Journal of surgical research 1995-11, Vol.59 (5), p.553-559
• Main Authors: Pappas, Peter J., Fallek, Steve R., Garcia, Ambrosia, Araki, Clifford T., Back, Thomas L., Durán, Walter N., Hobson, Robert W.
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers; Cytokines - blood; Dermatology; Hemodynamics; Humans; Leukocytes - physiology; Lymphocyte Activation; Male; Medical sciences; Middle Aged; Streptococcus - isolation & purification; Varicose Ulcer - blood; Varicose Ulcer - microbiology; Varicose Ulcer - physiopathology; Vascular disorders of the skin
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1995.1205

Alteration in leukocyte activation has been implicated as an etiological factor in the development of chronic venous stasis ulcers (CVSU). The purpose of this study was to determine differences in expression of cell surface activation markers on circulating leukocytes and systemic, soluble, serum cytokine levels between healthy controls and patients with CVSU. Twenty-three patients were separated into two groups. Group I consisted of 12 healthy, adult, age-matched male patients with no venous disease. Group II consisted of 11 adult male patients with CVSU who underwent air plethysmography (APG) and duplex scanning to determine the severity of venous insufficiency. All patients had measurements of systemic, serum-based, soluble IL-1β, IL-2, IL-6, TNF-α, and β2 microglobulin levels. Using fluorescence flow cytometry, we measured the percentage of lymphocytes (CD3), monocytes (CD14), and granulocytes (CD15) expressing various cell surface activation markers. By APG and duplex scan, all group II patients exhibited venous insufficiency, with a mean venous filling index of 6.9 ± 3.9 sec. Relative to group I, group II patients demonstrated a decreased expression of the CD3+/DR+ (13.3 ± 1.5, P ⩽ 0.01) and CD3+/CD38+ (31.1 ± 2.1, P ⩽ 0.04) markers on T-lymphocytes and an increased expression of CD14+/CD38+ (99.6 ± 0.2, P ⩽ 0.008) markers on monocytes. Circulating neutrophils showed no evidence of activation. In addition, a significant elevation in the T-helper to T-suppressor ratio (2.9 ± 0.6, P ⩽ 0.0001) between groups I and II was observed. IL6 was elevated in group II, while TNF-α, IL-1β, IL-2, and β-2 microglobulin demonstrated no significant difference between groups. Our data demonstrate a down-regulation of CD3+/DR+ and CD3+/CD38+ markers on circulating T-lymphocytes, increased activation of CD14+/CD38+ circulating monocytes, and increased levels of soluble serum IL-6 in the systemic circulation of group II patients. The lack of systemic neutrophil activation suggests that their involvement in the pathogenesis of CVSU occurs locally in the microcirculatory environment of the affected limb. These observations also suggest that the ulcer itself may cause cellular dysfunction.