Doxycycline speeds up healing of chronic venous ulcers

Abstract

Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Sixty-four patients with venous ulcers were recruited in a 22-month period. All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 32 persons in each (groups A and B). Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B received basic treatment only. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a higher healing rate compared with group B. In group B, the lower healing rate was related to higher levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular endothelial growth factor, documented in plasma; wound fluid and biopsies executed and compared between both groups. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti-inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.

Keywords: Chronic venous leg ulcers; Doxycycline; Metalloproteinase-9; Neutrophil gelatinase-associated lipocalin; Wound healing.

© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Figures

Figure 1

Plasma levels of matrix metalloproteinase‐9 (MMP‐9) (up) and neutrophil gelatinase‐associated lipocalin (NGAL) (down) evaluated through enzyme‐linked immunosorbent assay (ELISA) test in both tetracycline‐treated (group A) and non treated patients (group B). The results represent mean ± SEM. **P < 0·01; *P < 0·05.

Figure 2

Wound fluid levels of matrix metalloproteinase‐9 (MMP‐9) (up) and neutrophil gelatinase‐associated lipocalin (NGAL) (down) evaluated through enzyme‐linked immunosorbent assay (ELISA) test in both tetracycline‐treated (group A) and non‐treated patients (group B). The results represent mean ± SEM. **P < 0·01; *P < 0·05.

Figure 3

Tissue expression of matrix metalloproteinase‐9 (MMP‐9) (up) and neutrophil gelatinase‐associated lipocalin (NGAL) (down) in both doxycycline‐treated (group A) and non‐treated patients (group B). The results represent mean ± SEM. **P < 0·01; *P < 0·05.

Figure 4

Plasma (up) and wound fluid (down) levels of vascular endothelial growth factor (VEGF) evaluated through enzyme‐linked immunosorbent assay (ELISA) test in both tetracycline‐treated (group A) and non‐treated patients (group B). The results represent mean ± SEM. **P < 0·01; *P < 0·05.