Abstract
Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies. The aim of this article is to evaluate the effects of wound etiology on a panel of circulating cytokines in patients with non-healing wounds of the lower extremities. This prospective case-control study involved 104 individuals: healthy elderly people (n = 46) and patients with diabetes and/or cardiovascular disease (n = 58; among them 38 with chronic wounds of venous, ischemic or neurotrophic etiology). Selected serum cytokines - i.e. IL-1β, IL-4, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-BB - were measured using the Luminex platform. Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, MCP-1 and G-CSF while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and GM-CSF. Among diseased elderly people, having wounds was associated with increased levels of IL-1β, IL-4, IL-6, IL-8, FGF-2, MIP-1α, PDGF-BB, and VEGF-A. Interleukin 1β elevation was a sole independent predictor of chronic wounds with an odds ratio (OR) of 6.3. Cytokines in healthy seniors were loosely interrelated, while the levels of cytokines in diseased patients with wounds displayed a tight pattern of association. When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and VEGF-A was disrupted in neurotrophic wounds. The results presented herein may improve our understanding of the pathomechanisms which lead to chronic wounds and of the effects they exert on a systemic level, as well as providing potential targets for more effective therapies.
Highlights
Conditions such as diabetes or atherosclerosis can disturb blood flow, damage blood vessels, and, if severe, result in ulcerations or gangrene, most often located in the lower limbs
Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte colony-stimulating factor (G-CSF) while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF)
When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and vascular endothelial growth factor (VEGF)-A was disrupted in neurotrophic wounds
Summary
Conditions such as diabetes or atherosclerosis can disturb blood flow, damage blood vessels, and, if severe, result in ulcerations or gangrene, most often located in the lower limbs. Taking into account the prevalence of obesity, diabetes and cardiovascular disease among elderly people, chronic wounds of the lower extremities are becoming a growing socioeconomic problem for aging societies. Persistent, frequent and often infected, they reduce quality of life, rendering afflicted persons disabled and in need of repeated hospitalization.[1,2] Non-healing wounds are a major cause of morbidity and mortality and are responsible for over 80% of diabetes-associated amputations.[3,4] Chronic wounds are currently estimated to affect up to 2% of the general population but − because their prevalence is increasing − it is predicted that they will affect 1⁄4 of elderly people by the year 2050.5. Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies
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