The relationship between cytokine concentrations and wound healing in chronic venous ulceration.
OBJECTIVE
The importance of wound cytokine function in chronic venous leg ulcers remains poorly understood. This study evaluated the relationship between local and systemic concentrations of wound cytokines and wound healing in patients with chronic venous ulceration.


METHODS
This prospective observational study was set in a community- and hospital-based leg ulcer clinic. Consecutive patients with chronic leg ulceration and ankle-brachial pressure index >0.85 were prospectively investigated. All patients were treated with multilayer compression bandaging. Wound fluid and venous blood samples were collected at recruitment and 5 weeks later. In the wound fluid and venous blood, cytokines and factors reflecting the processes of inflammation (interleukin 1beta, tumor necrosis factor-alpha), proteolysis (matrix metalloproteinases-2 and -9), angiogenesis (basic fibroblast growth factor [bFGF], vascular endothelial growth factor), and fibrosis (transforming growth factor-beta(1) [TGFbeta(1)]) were measured. Ulcer healing was assessed using digital planimetry at both assessments.


RESULTS
The study comprised 80 patients (43 men, 37 women). Median (range) ulcer size reduced from 4.4 (0.1-142.4) cm(2) to 2.2 (0-135.5) cm(2) after 5 weeks (P < .001; Wilcoxon signed rank), although 17 of 80 ulcers increased in size. The volume of wound fluid collected strongly correlated with ulcer size (Spearman rank = 0.801, P < .01). Initial wound fluid concentrations of bFGF correlated with ulcer size (Pearson coefficient = 0.641, P < .01), and changes in wound fluid TGFbeta(1) concentrations inversely correlated with changes in ulcer size (Spearman rank = -0.645, P = .032). There were no significant correlations between changes in other factors and ulcer healing. Wound fluid and serum cytokine concentrations correlated poorly.


CONCLUSIONS
Wound fluid collection volume correlates with ulcer size. Ulcer healing correlated with increased concentrations of TGFbeta(1), possibly reflecting increased fibrogenesis in the proliferating wound. Aside from this, there was a large variation in wound and serum cytokine levels that largely limits their usefulness as markers of healing.
Gohel
Manjit S
MS
Department of Vascular Surgery, Cheltenham General Hospital, Gloucestershire, United Kingdom.
Windhaber
Robin A J
RA
Tarlton
John F
JF
Whyman
Mark R
MR
Poskitt
Keith R
KR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005122:Exudates and Transudates / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D053828:Stockings, Compression; D016896:Treatment Outcome; D014647:Varicose Ulcer / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D014945:Wound Healing
D015415:Biomarkers; D016207:Cytokines