Tumor necrosis factor-alfa in nonhealing venous leg ulcers

Carlos A. Charles, Paolo Romanelli, Zuleika Bonilla Martinez, Fangchao Ma, Brenda Roberts, Robert Kirsner

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: 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 (TNFα), which may be implicated in wound chronicity. Objective: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFα as compared to normal skin. Methods: 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 TNFα. Qualitative and quantitative comparisons were made for the presence of TNFα receptor in all tissue samples, specifically comparing the presence of TNFα in nonhealing venous leg ulcer samples versus normal skin. Results: The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFα 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). Limitations: The small sample size may mitigate the clinical implications of findings. Conclusions: Increased levels of TNFα 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.

Original languageEnglish
Pages (from-to)951-955
Number of pages5
JournalJournal of the American Academy of Dermatology
Volume60
Issue number6
DOIs
StatePublished - Jun 1 2009

Fingerprint

Varicose Ulcer
Leg Ulcer
Tumor Necrosis Factor-alpha
Skin
Wounds and Injuries
Tumor Necrosis Factor Receptors
Forearm
Sample Size
Formaldehyde
Ulcer
Lower Extremity
Immunohistochemistry
Staining and Labeling
Cytokines
Inflammation
Biopsy

ASJC Scopus subject areas

  • Dermatology

Cite this

Tumor necrosis factor-alfa in nonhealing venous leg ulcers. / Charles, Carlos A.; Romanelli, Paolo; Martinez, Zuleika Bonilla; Ma, Fangchao; Roberts, Brenda; Kirsner, Robert.

In: Journal of the American Academy of Dermatology, Vol. 60, No. 6, 01.06.2009, p. 951-955.

Research output: Contribution to journalArticle

Charles, Carlos A. ; Romanelli, Paolo ; Martinez, Zuleika Bonilla ; Ma, Fangchao ; Roberts, Brenda ; Kirsner, Robert. / Tumor necrosis factor-alfa in nonhealing venous leg ulcers. In: Journal of the American Academy of Dermatology. 2009 ; Vol. 60, No. 6. pp. 951-955.
@article{b322f32cd61b4a5080aa5f89aeb680a7,
title = "Tumor necrosis factor-alfa in nonhealing venous leg ulcers",
abstract = "Background: 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 (TNFα), which may be implicated in wound chronicity. Objective: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFα as compared to normal skin. Methods: 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 TNFα. Qualitative and quantitative comparisons were made for the presence of TNFα receptor in all tissue samples, specifically comparing the presence of TNFα in nonhealing venous leg ulcer samples versus normal skin. Results: The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFα 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). Limitations: The small sample size may mitigate the clinical implications of findings. Conclusions: Increased levels of TNFα 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.",
author = "Charles, {Carlos A.} and Paolo Romanelli and Martinez, {Zuleika Bonilla} and Fangchao Ma and Brenda Roberts and Robert Kirsner",
year = "2009",
month = "6",
day = "1",
doi = "10.1016/j.jaad.2008.09.012",
language = "English",
volume = "60",
pages = "951--955",
journal = "Journal of the American Academy of Dermatology",
issn = "0190-9622",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Tumor necrosis factor-alfa in nonhealing venous leg ulcers

AU - Charles, Carlos A.

AU - Romanelli, Paolo

AU - Martinez, Zuleika Bonilla

AU - Ma, Fangchao

AU - Roberts, Brenda

AU - Kirsner, Robert

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Background: 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 (TNFα), which may be implicated in wound chronicity. Objective: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFα as compared to normal skin. Methods: 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 TNFα. Qualitative and quantitative comparisons were made for the presence of TNFα receptor in all tissue samples, specifically comparing the presence of TNFα in nonhealing venous leg ulcer samples versus normal skin. Results: The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFα 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). Limitations: The small sample size may mitigate the clinical implications of findings. Conclusions: Increased levels of TNFα 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.

AB - Background: 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 (TNFα), which may be implicated in wound chronicity. Objective: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFα as compared to normal skin. Methods: 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 TNFα. Qualitative and quantitative comparisons were made for the presence of TNFα receptor in all tissue samples, specifically comparing the presence of TNFα in nonhealing venous leg ulcer samples versus normal skin. Results: The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFα 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). Limitations: The small sample size may mitigate the clinical implications of findings. Conclusions: Increased levels of TNFα 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.

UR - http://www.scopus.com/inward/record.url?scp=67349202787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349202787&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2008.09.012

DO - 10.1016/j.jaad.2008.09.012

M3 - Article

C2 - 19344978

AN - SCOPUS:67349202787

VL - 60

SP - 951

EP - 955

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

IS - 6

ER -