Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor,
tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute
inflammation and regulators of the wound healing process. The aim of this systematic review was to determine the local and systemic involvement of the
MMP-9/TIMP-1 system following
burn injury. Two databases (Scopus and MEDLINE) were searched for all studies reporting MMP-9 and/or
TIMP-1 after
burn injury. Based on our eligibility criteria, we reviewed 24 studies involving 508
burns patients in 11 clinical studies and 367 animals in 13 preclinical studies. Local, systemic, and peripheral gene expression,
protein levels and activity of MMP-9 and
TIMP-1 were assessed. Increased MMP-9 was reported at the site of injury early after
burn trauma in all studies, and remained elevated in non-healing
wounds. Increased
TIMP-1 expression in
burn wounds occurred later than MMP-9, and was persistent in hypertrophic
burn scars. Similar to local expression, systemic MMP-9 and
TIMP-1 concentrations were significantly elevated after
burn injury in response to upregulation of proinflammatory
cytokines. While no association was found between systemic MMP-9 concentration and extent of injury or outcome, serum or plasma
TIMP-1 showed good correlation with survival and
burn severity. This review also found evidence of the
MMP-9/TIMP-1 system contributing to secondary tissue damage distant from the
burn site, including
burn-associated musculoskeletal damage and
acute lung injury. In addition, increased MMP-9 synthesis and activity in the brain after peripheral
burn may lead to blood-brain barrier dysfunction and
cerebral edema, a significant contributor to mortality. This systematic review provides an overview of the available evidence of the role of MMP-9 and
TIMP-1 in
burn injury pathophysiology and finds that
TIMP-1 may be a promising
biomarker in outcome prognostication of
burns patients. Large-scale studies of both pediatric and adult
burns patients with increased female representation and repeated sampling are recommended to validate the reliability of
TIMP-1 as a prognostic marker following
burn injury.