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Anti-inflammatory Effects of Clostridial Collagenase

Results from In Vitro and Clinical Studies

Richard C. Galperin Private practice, Dallas, TX.

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Darrell L. Lange Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Sarah J. Ramsay Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Lei Shi Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Kathy A. Weedon Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Nancy M. Hudson Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Jaime E. Dickerson Jr Smith & Nephew Biotherapeutics, Fort Worth, TX.
Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX.

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D. Innes Cargill Smith & Nephew Biotherapeutics, Fort Worth, TX.

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Herbert B. Slade Smith & Nephew Biotherapeutics, Fort Worth, TX.
Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, TX.

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Background

Digestion of collagen with clostridial collagenase (CC) produces peptides that can induce cellular responses consistent with wound healing in vivo. However, nonhealing human wounds are typically in a state of chronic inflammation. We evaluated the effects of CC on markers of inflammation in cell culture and wound fluid from diabetic patients.

Methods

Lipopolysaccharide-induced release of tumor necrosis factor-α and interleukin-6 from interferon-γ–activated THP-1 monocytes was measured in the presence or absence of CC or CC collagen digests. In the clinical study, 17 individuals with mildly inflamed diabetic foot ulcers were randomized to receive CC ointment (CCO) or hydrogel. Weekly assessments included wound appearance and measurements. Wound exudate was collected at baseline and at 2 and 4 weeks of treatment. A multiplex assay was used to measure levels of analytes, including those associated with inflammation and with inflammation resolution.

Results

Lower levels of tumor necrosis factor-α and interleukin-6 were found in media of cells cultured with CC or CC digests of collagen type I or III than for untreated lipopolysaccharide controls (P < .05). Clinically, CCO and hydrogel resulted in improvement in wound appearance and a decrease in mean wound area. The CCO, but not the hydrogel, was found to increase the level of analytes associated with resolution of inflammation while decreasing those associated with inflammation. There was a general correlation between resolution of inflammation and healing.

Conclusions

These results support a hypothesis that debridement with CCO is associated with decreased inflammation and greater progress toward healing.

Corresponding author: Jaime E. Dickerson, Jr, PhD, 3909 Hulen St, Fort Worth, TX 76107. (E-mail: jaime.dickerson@smith-nephew.com)