Purpose: With clinical progression of chronic venous insufficiency (CVI), dermal infiltration of mononuclear cells increases. Because these cells regulate chronic inflammatory responses and modulate wound healing, cellular dysfunction could explain alterations in wound healing with CVI. The purpose of this study was to determine whether monocytes in patients with CVI are dysfunctional.
Methods: Mononuclear cell function was measured as the degree of proliferation in response to a mitogenic challenge. Fifty patients were separated into four groups: group 1, 14 patients with normal limbs; group 2, 10 patients with class 2 CVI; group 3, 15 patients with active venous ulcers; group 4, 11 patients with healed venous ulcers and current evidence of lipodermatosclerosis. Duplex scanning and air plethysmography correlated with the clinical classification of CVI. Systemically circulating monocytes and lymphocytes were obtained by antecubital venipuncture from groups 1 to 4. Cells were cultured in the presence of staphylococcal enterotoxins A, B, C1, D, and E (mitogens) at 1, 8, 31, and 125 micrograms/well on the basis of previous dose-response experiments. Phytohemagglutinin (PHA), 5 micrograms/well, served as a control mitogen. The dose-response curves indicated that 8 micrograms/well elicited the greatest degree of cell proliferation. Proliferative responses at 8 micrograms/well were analyzed for statistical significance among groups 1 to 4. Comparisons among groups were performed by use of the nonparametric Mann Whitney U post tests and a one-tailed unpaired t test. Results were considered significant at p < or = 0.05.
Results: Proliferative responses to PHA indicate that lymphocytes and monocytes from patients with CVI are not globally depressed. However, patients in group 2 did not exhibit the same degree of proliferation to PHA as did groups 1, 3 and 4. Proliferative responses between groups 2 and 1 (44.38 +/- 43.9 vs 118.87 +/- 27.1, p < or = 0.05) and groups 2 and 3 (44.38 +/- 43.9 vs 105.95 +/- 60.99, p < or = 0.05) were significant. Challenges with staphylococcal enterotoxin A and B reveal significant diminution of proliferative responses in groups 2 (42.73 +/- 11.55, p < or = 0.05) and 3 (45.57 +/- 9.1, p < or = 0.05) and groups 3 (36.81 +/- 6.9, p < or = 0.05) and 4 (35.04 +/- 7.5, p < or = 0.05), compared with staphylococcal enterotoxin A controls (68.68 +/- 9.9) and staphylococcal enterotoxin B controls (66.25 +/- 13.56), respectively. A trend of diminished mononuclear cell function with progression of CVI was observed with staphylococcal enterotoxins B, C1, D, and E, strongly suggesting biologic significance. Furthermore, patients with lipodermatosclerosis uniformly exhibited the poorest proliferative responses.
Conclusions: Deterioration of mononuclear cell function is associated with CVI. A trend of diminishing proliferative responses with clinical disease progression is observed and suggests biologic significance. The decreased capacity for mononuclear cell proliferation in response to various challenges may manifest itself clinically as poor and prolonged wound healing.