title: Anti-inflammatory Effects of Clostridial Collagenase Results from In Vitro and Clinical Studies.
abstract: 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.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Galperin
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Lange
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ramsay
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Weedon
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hudson
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Dickerson
authors.forename: D Innes
authors.initials: DI
authors.lastname: Cargill
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Slade
mesh_terms: D002478:Cells, Cultured; D017364:Collagenases / Q000627:therapeutic use*; D003646:Debridement / Q000379:methods*; D017719:Diabetic Foot / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014945:Wound Healing
chemical_list: D017364:Collagenases