DIMINISHED MONONUCLEAR CELL-FUNCTION IS ASSOCIATED WITH CHRONIC VENOUS INSUFFICIENCY

Purpose: With clinical progression of chronic venous insufficiency (CV I), dermal infiltration of mononuclear cells increases. Because these cells regulate chronic inflammatory responses and modulate wound heali ng, cellular dysfunction could explain alterations in wound healing wi th CVI. The purpose of this study was to determine whether monocytes i n patients with CVI are dysfunctional. Methods: Mononuclear cell funct ion was measured as the degree of proliferation in response to a mitog enic challenge. Fifty patients were separated into four groups: group 1, 14 patients with normal limbs; group 2, 10 patients with class 2 CV I; group 3, 15 patients with active venous ulcers; group 4, 11 patient s with healed venous ulcers and current evidence of lipodermatoscleros is. Duplex scanning and air plethysmography correlated with the clinic al classification of CVI, Systemically circulating monocytes and lymph ocytes were obtained by antecubital venipuncture from groups 1 to 4. C ells were cultured in the presence of staphylococcal enterotoxins A, B , C-1, D, and E (mitogens) at 1, 8, 31, and 125 mu g/well on the basis of previous dose-response experiments. Phytohemagglutinin (PHA), 5 mu g/well, served as a control mitogen. The dose-response curves indicat ed that 8 mu g/well elicited the greatest degree of cell proliferation . Proliferative responses at 8 mu g/well were analyzed for statistical significance among groups 1 to 4. Comparisons among groups were perfo rmed by use of the nonparametric Mann Whitney U post tests and a one-t ailed unpaired t test. Results were considered significant at p less t han or equal to 0.05. Results: Proliferative responses to PHA indicate that lymphocytes and monocytes from patients with CVI are not globall y depressed. However, patients in group 2 did nor exhibit the same deg ree of proliferation to PHA as did groups 1, 3, and 4. Proliferative r esponses between groups 2 and 1 (44.38 +/- 43.9 vs 118.87 +/- 27.1, p less than or equal to 0.05) and groups 2 and 3 (44.38 +/- 43.9 vs 105. 95 +/- 60.99, p less than or equal to 0.05) were significant. Challeng es with staphylococcal enterotoxin A and B reveal significant diminuti on of proliferative responses in groups 2 (42.73 +/- 11.55, p less tha n or equal to 0.05) and 3 (45.57 +/- 9.1, p less than or equal to 0.05 ) and groups 3 (36.81 +/- 6.9, p less than or equal to 0.05) and 4 (35 .04 +/- 7.5, p less than or equal to 0.05), compared with staphylococc al enterotoxin A controls (68.68 +/- 9.9) and staphylococcal enterotox in B controls (66.25 +/- 13.56), respectively. A trend of diminished m ononuclear cell function with progression of CVI was observed with sta phylococcal enterotoxins B, C-1, D, and E, strongly suggesting biologi c significance. Furthermore, patients with Lipodermatosclerosis unifor mly exhibited the poorest proliferative responses. Conclusions: Deteri oration of mononuclear cell function is associated with CVI. A trend o f diminishing proliferative responses with clinical disease progressio n is observed and suggests biologic significance. The decreased capaci ty for mononuclear cell proliferation in response to various challenge s may manifest itself clinically as poor and prolonged wound healing.