Tumor necrosis factor–alfa in nonhealing venous leg ulcers

Abstract

Venous leg ulcers are responsible for more than half of all lower extremity ulcerations, affecting more than one million Americans annually. Studies have demonstrated alterations in levels of proinflammatory cytokines in patients with chronic wounds, including tumor necrosis factor-alfa (TNFalpha), which may be implicated in wound chronicity. To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFalpha as compared to normal skin. Five patients with nonhealing healing chronic venous leg ulcers were recruited. Two 4-mm punch biopsy specimens were obtained: one from the wound margin and one from noninvolved, non-sun exposed normal skin on the flexor aspect of the forearm. Tissue samples were processed using fixed with formalin stained by immunohistochemistry for TNFalpha. Qualitative and quantitative comparisons were made for the presence of TNFalpha receptor in all tissue samples, specifically comparing the presence of TNFalpha in nonhealing venous leg ulcer samples versus normal skin. The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFalpha was significantly less in the two nonhealing venous leg ulcers that were present for the shortest duration compared to the other ulcers of longer duration (P = .048). The small sample size may mitigate the clinical implications of findings. Increased levels of TNFalpha in nonhealing venous leg ulcers, especially those of longer duration, implies that excessive inflammation may be causal in wound chronicity and suggests potential therapeutic alternatives.