Abstract

Differences in Inflammatory Cytokine Levels between Patients with Varying Severity of Chronic Venous Insufficiency

Lark G Guss, Srimanasi Javvaji, Jamie Case, Bethany Barrick BS, Kathryn N Schaefer, Ryan Gilbertson BS, Jill Waalen, Hugh T Greenway and Leland B Housman

Objective: Several studies have found that protein concentrations of inflammatory cytokines are significantly increased in tissue and serum from patients with chronic venous insufficiency (CVI) relative to that of healthy controls. We sought to determine whether inflammatory protein concentrations differ between patients with moderate clinical disease, classified as clinical, etiology, anatomy, pathophysiology (CEAP) Classes 2 and 3, and more severe clinical disease, classified as CEAP Class 4.
Methods: Twenty patients with abnormal venous function were included in the study. Blood from a competent leg vein and from an incompetent superficial vein was collected in addition to incompetent vein tissue extracted through a phlebectomy procedure. Cytokine levels of venous tissue lysate and serum samples were determined using a multiplex assay.
Results: Thirteen patients (65%) were classified as clinical CEAP Class 2 or 3, with seven patients (35%) falling into the more severe Class 4 category. Twenty-seven cytokines were measured. Serum isolated from normal veins had significantly higher levels of IFN-gamma in patients with Classes 2 and 3 than Class 4 disease (95.17 pg/mL vs. 71.97 pg/mL; p=0.036). In serum from incompetent veins, IFN-gamma concentrations averaged 95.47 pg/mL in Class 2 and 3 patients and 76.97 pg/mL in Class 4 patients (p=0.048). Eotaxin levels from diseased vein tissue averaged 3.37 pg/mL in Classes 2 and 3 patients, and 1.57 pg/mL in Class 4 patients (p=0.037). IP-10 levels in diseased vein tissue was also significantly less in Class 4 patients at 74.20 pg/mL in Class 2 and 3 patients versus 31.06 pg/mL in Class 4 patients (p=0.004).
Conclusion: Despite several studies documenting increased inflammatory cytokines in patients with CVI, our study shows that those patients with more severe disease have significantly lower levels of several inflammatory cytokines. Thus, particular inflammatory cytokines may function in a reparative capacity following tissue injury or as a control mechanism to inhibit further tissue destruction.