Cytokine and protease levels in healing and non‐healing chronic venous leg ulcers

Abstract

Leg ulcers present a common and recurring problem in older people creating discomfort and distress for the patient and a great cost to the health care services. Cultured keratinocyte grafts have been used by many investigators to stimulate healing of chronic venous ulcers. It has been proposed that they may do this by producing cytokines which modulate the healing process. However, the types and levels of cytokines in the leg ulcer fluid before and during healing are not known. Wound fluid was collected from venous leg ulcers in 18 patients beneath occlusive Tegaderm dressing for 4 to 6 h. The leg ulcers were divided on clinical criteria into 'healing' and 'non-healing'. PDGF-AB, GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and bFGF were measured by ELISA and the levels of IL-1 alpha, IL-1 beta and IL-6 were also measured using biological assays. The effect of leg ulcer wound fluid on fibroblast and keratinocyte proliferation was measured indirectly by 3H-thymidine incorporation and MTT assay. Total protein, albumin levels, fibronectin degrading activity and collagenase activity, both active and latent were measured. No statistically significant differences in the levels of cytokines or collagenase were identified between healing and non-healing leg ulcers in the sample of leg ulcers studied. However, this study does give valuable information concerning the levels of cytokines and collagenase in chronic leg ulcer wound fluid.

Dose-Dependent Impairment of Collagen Deposition by Topical Granulocyte-Macrophage Colony-Stimulating Factor in Human Experimental Wounds

“…38 In this study, GM-CSF was administered at concentrations from 0.1 to 75 g/mL, representing values 5,000 to 4 million times higher, although the local endogenous GM-CSF levels rise about 100-fold at an inflammatory site to 1,000 to 3,000 pg/mL. 15,33,39 In the study by Ure et al, 15 intradermal injections in the thigh of healthy volunteers with 20 g GM-CSF 1 and 4 days after wounding resulted in elevated GM-CSF levels not only in the treated leg but also (albeit less so) in the wound on the contralateral leg not injected with GM-CSF. This finding supports our biochemical data of reduced collagen deposition also in the control ePTFE tubes as a distant effect of GM-CSF.…”

Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers

“…Several studies on cytokine levels in wound fluids from CVLUs have been conducted, but results are inconclusive and more studies are warranted [3,[12][13][14][15][16]. In particular more knowledge is needed on how different cytokines are expressed in chronic wounds at different time-points during the healing process.…”

Risk Factors Associated With the Failure of a Venous Leg Ulcer to Heal

“…Studies comparing acute and chronic wounds have demonstrated that differences between them do exist, and it is possible that these differences become more dramatic as a wound ages, eventually reaching a critical point at which healing is less likely to occur. [41][42][43][44][45][46][47] The relationship between wound duration and wound size is further complicated by an interaction between these 2 risk factors. A basic assumption inherent in regression models is that the association of any given variable with the outcome is the same for all values of any other given variable.…”