ROLE OF LEUKOCYTE ACTIVATION IN PATIENTS WITH VENOUS STASIS ULCERS

Alteration in leukocyte activation has been implicated as an etiologic al factor in the development of chronic venous stasis ulcers (CVSU). T he purpose of this study was to determine differences in expression of cell surface activation markers on circulating leukocytes and systemi c, soluble, serum cytokine levels between healthy controls and patient s with CVSU. Twenty-three patients were separated into two groups. Gro up I consisted of 12 healthy, adult, age-matched male patients with no venous disease. Group II consisted of 11 adult male patients with CVS U who underwent air plethysmography (APG) and duplex scanning to deter mine the severity of venous insufficiency. All patients had measuremen ts of systemic, serum-based, soluble IL-1 beta, IL-2, IL-6, TNF-alpha, and beta 2 micro-globulin levels. Using fluorescence flow cytometry, we measured the percentage of lymphocytes (CD3), monocytes (CD14), and granulocytes (CD15) expressing various cell surface activation marker s. By APG and duplex scan, all group II patients exhibited venous insu fficiency, with a mean venous filling index of 6.9 +/- 3.9 sec. Relati ve to group I, group II patients demonstrated a decreased expression o f the CD3+/DR+ (13.3 +/- 1.5, P less than or equal to 0.01) and CD3+/C D38+ (31.1 +/- 2.1, P less than or equal to 0.04) markers on T-lymphoc ytes and an increased expression of CD14+/CD38+ (99.6 +/- 0.2, P less than or equal to 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 less than or eq ual to 0.0001) between groups I and II was observed. IL-6 was elevated in group II, while TNF-alpha, IL-1 beta, IL-2, and beta-2 microglobul in demonstrated no significant difference between groups. Our data dem onstrate a down-regulation of CD3+/DR+ and CD3+/CD38+ markers on circu lating 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 acti vation suggests that their involvement in the pathogenesis of CVSU occ urs locally in the microcirculatory environment of the affected limb. These observations also suggest that the ulcer itself may cause cellul ar dysfunction. (C) 1995 Academic Press,Inc.