interleukin-8 and Varicose-Ulcer

Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.. This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.. Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.. Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.

Topics: Administration, Topical; Aged; Aged, 80 and over; Blood Platelets; Chronic Disease; Double-Blind Method; Female; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Humans; Immunologic Factors; Interleukin-8; Male; Middle Aged; Tissue Inhibitor of Metalloproteinase-1; Varicose Ulcer; Vascular Endothelial Growth Factor A; Wound Healing

Wound fluid collected from chronic wounds may be used as a simple gauge of the processes taking place in the tissue. There is lack of information on the optimal conditions for wound fluid procurement. We have studied possible diurnal variations and duration of wound fluid accumulation using retentive hydrophobic foam on the levels of prototypic cytokines [interleukin (IL)-1α, IL-1β], a chemokine (IL-8) and proteinases [matrix metalloproteinase (MMP)-9] in 23 chronic venous leg ulcer patients. Bioactivity of 1 and 24 h wound fluids, and serum was also compared. There were no significant temporal changes in the levels of the above-mentioned four proteins, when comparing three consecutive 8-h intervals starting from 0800 that in turn did not differ significantly with the 24-h collection levels. IL-1α, IL-1β and IL-8 levels were higher (p < 0.05) in 24 h compared with 1 h wound fluids, whereas MMP-9 levels were insensitive to the length of collection. The 24 h wound fluids did not elicit DNA synthesis in adult human dermal fibroblasts in contrast to the 1 h wound fluids (p = 0.046) and serum (p = 0.036). The polyurethane foam alone had no significant effects on the concentration of the examined analytes. The length of collection is critical when monitoring cytokine/chemokine and bioactivity levels of chronic wound fluid. The removal of accumulating unfavorable factors in chronic wound fluid may be important in wound management.

Topics: Aged; Aged, 80 and over; Bandages; Circadian Rhythm; Cohort Studies; DNA; Female; Fibroblasts; Humans; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Polyurethanes; Reproducibility of Results; Time Factors; Varicose Ulcer; Wound Healing

The molecular pathogenesis of chronic skin wounds is complex and not fully understood. Although these wounds are often characterized as being in a state of persistent inflammation, the impact and participation of the innate immune responses in sustaining this inflammation needs further investigation.. We investigated the cytokine profiles, Toll-like receptor (TLR)-stimulating activities and the levels of the antibacterial peptide Lipocalin-2 (Lcn-2) in a series of healing and non-healing chronic venous leg ulcers (CVLUs) through a study time of 8 weeks.. Wound fluids from healing and non-healing CVLUs were run on a Human Cytokine Antibody Array, and Lcn-2 levels measured with ELISA. HEK 293 cells transfected with TLR2 or TLR4 and their respective co-receptors, and human peripheral blood monocytes were then stimulated with the wound fluids from healing and non-healing venous leg ulcers.. Healing wounds were associated with decreasing levels of IL-1alpha, IL-1beta and MIP-1delta, whereas in non-healing wounds decreasing levels of IL-8 and MIP-1alpha were found. Accordingly, wound fluid from non-healing CVLUs contained persistent Lcn-2 levels and TLR2- and TLR4-stimulating activities, while, in healing wounds, the TLR-stimulating activities decreased over time with significantly diminished levels of Lcn-2 (p<0.005).. Innate immune responses contribute to the chronic inflammation in non-healing CVLUs through participation of Toll-like receptors. The levels of the antimicrobial peptide Lcn-2 in wound fluids from these ulcers are elevated as a reflection of this contribution.

Topics: Acute-Phase Proteins; Cells, Cultured; Chemokine CCL3; Chronic Disease; Humans; Immunity, Innate; Interleukin-8; Kidney; Leukocytes, Mononuclear; Lipocalin-2; Lipocalins; Proto-Oncogene Proteins; Toll-Like Receptor 2; Toll-Like Receptor 4; Varicose Ulcer; Wound Healing

The objective was to determine the activation of white blood cells (WBCs) and endothelial cells in patients with healed venous ulcer and the influence of the standing position and of treatment with flavonoids. Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days. Blood samples were taken from arm and dorsal foot veins before and after standing for 30 minutes. Blood sampling was performed before treatment, after three days, one month and three months. The activation of WBCs was determined by measuring adhesion molecule CD11b and CD18 expression on the surface of granulocytes and monocytes. In addition, interleukin 6 (IL-6), IL-8, soluble E-selectin (sE-selectin), sL-selectin and sICAM-1 levels in serum were quantified. The results showed that standing did not influence any of the measured parameters significantly. Expression of CD11b adhesion molecules on granulocytes was significantly up-regulated (p = 0.044) after treatment with flavonoids for one month, but this increase was not significant (p = 0.056) two months after the treatment period compared with the baseline level. The expression of CD18 remained unchanged. Baseline expression of CD11b or CD18 on monocytes did not change significantly during the study period. Neither was any significant change observed in the levels of IL-6, IL-8 or the soluble adhesion molecules. It was concluded that flavonoid treatment for 30 days increased the expression of CD11b adhesion molecules on circulating granulocytes. No general effect on the inflammatory process could be observed as assessed by levels of cytokines and soluble adhesion molecules. Possible explanations for these findings could be that a decreased number of primed granulocytes leave the circulation due to a changed WBC/endothelial cell interaction or that flavonoids have a direct effect on granulocytes. Further studies are needed to clarify the mode of action of flavonoids in chronic venous disease.

Topics: Adult; Aged; CD18 Antigens; Diosmin; E-Selectin; Endothelium, Vascular; Female; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; L-Selectin; Male; Microcirculation; Middle Aged; Neutrophils; Statistics, Nonparametric; Varicose Ulcer