TIMP-1, MMP-2, MMP-9, and PIIINP as serum markers for skin fibrosis in patients following severe burn trauma.

Abstract

The wound-healing process of patients with severe burns often leads to the formation of extensive fibrotic scars. In this study, serum concentrations of tissue inhibitors of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and amino-terminal propeptide of procollagen type III (PIIINP) were measured by enzyme-linked immunosorbent assay as markers for excessive cicatrization in 22 patients with acute burn injuries. All patients were followed up for 6 months to determine a fibrotic reaction during the wound-healing process after operative treatment using the Burn Scar Index. Blood samples were drawn immediately before the operation; at postoperative days 1, 3, 7, and 14; and 1, 3, and 6 months after the operation. Twenty patients who underwent elective plastic surgical operations served as the control group. There was a significant increase (p < 0.05) of TIMP-1 in the burned patients by the third postoperative day. Later in the follow-up period, the serum concentrations remained at a significantly elevated level (p < 0.05) compared with preoperative values. In comparison with the control group, the postoperative serum concentrations of TIMP-1 of the burned patients were significantly higher (p < 0.05) at any time and correlated with the total body surface area burned at the third and seventh postoperative days (p < 0.05; r2 = 0.46 versus r2 = 0.53) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.65). Serum levels of MMP-2 and MMP-9 showed a significant elevation (p < 0.05) only between postoperative days 3 and 14 in patients with burn wounds. PIIINP increased significantly (p < 0.05) in the sera of the burned patients at postoperative day 3 and remained significantly elevated up to 6 months after injury. At any time after trauma, PIIINP serum levels were significantly higher (p < 0.05) in the burned patients than in the control group and correlated with the total body surface area burned at postoperative days 3 and 7 (p < 0.05; r2 = 0.41 versus r2 = 0.44) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.5). Obviously, the physiological balance between matrix metalloproteinases and their endogenous inhibitors is disturbed after burn trauma. The elevated systemic TIMP-1 concentration might contribute to tissue fibrosis, leading to pathological scar formation. The increase of PIIINP after thermal trauma indicates a fibrogenic component of wound healing.

• Authors: Dietmar Ulrich, Ernst-Magnus Noah, Dennis von Heimburg, Norbert Pallua
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 111 Issue 4 Pg. 1423-31 (Apr 01 2003) ISSN: 0032-1052 [Print] United States
• PMID: 12618601 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Peptide Fragments
• Procollagen
• Tissue Inhibitor of Metalloproteinase-1
• procollagen Type III-N-terminal peptide
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Biomarkers (blood)
• Burns (pathology)
• Cicatrix (blood, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Fibrosis
• Humans
• Male
• Matrix Metalloproteinase 2 (blood)
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Peptide Fragments (blood)
• Procollagen (blood)
• Skin (pathology)
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Wound Healing