Wound healing is a complex process resulting from an interplay of processes including coagulation, inflammation, angiogenesis, and epithelialization. The chemokine family has been shown to contain members that are potent regulators of many of these pathways. Because we have previously shown that chemokines "pool" in biologic wound dressings, we studied the levels of CXC and CC chemokines, along with key inflammatory mediators, serially from a group of patients undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had marked clinical healing of their ulcers (median 63.3% reduction in size) with two of 10 completely healed. Wound fluids extracted from dressings showed high levels of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward increases in the ratio of the sums of the angiogenic versus angiostatic CXC chemokines (p = 0.082) in the tissues collected from the center of the ulcers during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted for the most changes in wound fluid angiogenic chemokines, with significant differences both as compared with baseline levels and with patients' plasma level noted at various time points between weeks 0 and 8. The level of angiostatic chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell most significantly between weeks 0 and 3 as compared with plasma levels. The observed shift toward angiogenic CXC chemokines suggests that effective healing in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a state more conducive to epithelialization,characteristic of the proliferative phase of wound healing. CC chemokines were also elevated at baseline in the wound fluid samples as compared with the patients' plasma levels. Macrophage inflammatory protein-1 (3 and regulated on activation, normal T expressed and secreted (RANTES) levels decreased with healing, whereas there were significant increases in the tissue levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or = 0.05 for both). Coincident with these changes was a steady increase in the ratio of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center tissues, which also correlated with healing (p < 0 .05) as compared with a decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids. These findings suggest that advanced wound care techniques help move the ulcer from a chronic inflammatory state into one more characteristic of the late inflammatory/early proliferative phase of wound healing. Chemokines may play a critical role in the pathogenesis of chronic venous ulcers through their effects on angiogenesis and/or the progression of inflammatory reactions at the site of injury.

译文

伤口愈合是一个复杂的过程,包括凝血、炎症、血管生成和上皮化。趋化因子家族已被证明包含许多这些途径的有效调节剂。因为我们以前已经表明趋化因子在生物伤口敷料中 “聚集”,所以我们连续研究了一组接受慢性静脉腿部溃疡治疗的患者的CXC和CC趋化因子以及关键炎症介质的水平。8周后,所有患者的溃疡临床愈合明显 (中位63.3% 缩小),其中10例中有2例完全愈合。从敷料中提取的伤口液显示出高水平的血小板因子-4和干扰素-γ 诱导蛋白,在伤口闭合期间从溃疡中心收集的组织中,血管生成与血管抑制CXC趋化因子 (p = 0.082) 的总和比率呈增加趋势。中性粒细胞激活肽-2和interleukin-8占伤口流体血管生成趋化因子的最大变化,与基线水平和患者血浆水平相比,在第0周和第8周之间的不同时间点存在显着差异。与血浆水平相比,血管抑制趋化因子,干扰素y诱导蛋白10和血小板活化4的水平在第0周和第3周之间下降最明显。观察到的向血管生成CXC趋化因子的转变表明,慢性静脉功能不全溃疡的有效愈合似乎使溃疡床 “移至” 更有利于上皮形成的状态,这是伤口愈合增生期的特征。与患者血浆水平相比,伤口液体样品中的CC趋化因子在基线时也升高。巨噬细胞炎性蛋白-1 (3) 和受激活调节,正常T表达和分泌 (RANTES) 水平随愈合而降低,而在治疗的前4周内,单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1 a的组织水平显着增加 (两者p <或 = 0.05)。与这些变化同时发生的是,interleukin-1 R/interleukin-1受体拮抗剂蛋白的比例在溃疡中心组织,与溃疡边缘的比率降低相比,这也与愈合相关 (p <0.05),和伤口液体中的双相反应。这些发现表明,先进的伤口护理技术有助于将溃疡从慢性炎症状态转移到伤口愈合的晚期炎症/早期增生期的另一个特征。趋化因子可能通过其对血管生成的影响在慢性静脉溃疡的发病机理中发挥关键作用和/或损伤部位炎症反应的进展。

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