Abstract
A major complication associated with burn injury is delayed wound healing. While healing of the burn injury site is essential, healing of distal injury sites caused by surgical interventions and other processes also is important. The impact of burn injury on healing of these distal wound sites is not understood clearly. To study this, mice were subjected to major burn injury or a sham procedure. Immediately following, excisional wounds were made on the dorsal surface caudal to the burn site and wound closure was monitored over a 7-d period by planimetry. In a second series of experiments, plasma and excisional wounds were collected for in vitro analysis of cyto- and chemokine levels, L-arginine metabolism, and hypoxia-inducible factor (HIF)-1alpha expression. At 1-7 d post-injury, a significant inflammatory response was evident in both groups, but the healing process was delayed in the burn-injured mice. At 3 d post-injury, wound levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and keratinocyte-derived chemokine were suppressed in the burn group. This difference in the wound inflammatory response was independent of changes in L-arginine metabolism (nitrate levels, inducible nitric oxide synthase expression, arginase activity), but correlated with a marked reduction in HIF-1alpha protein levels. In conclusion, these findings suggest that HIF-1alpha and the inflammatory response play a significant role in wound healing, and reduced levels of HIF-1alpha contribute to the impaired healing response post-burn.
Highlights
Complications induced by burn injury include immunosuppression, sepsis, and delayed wound healing
Plasma samples were collected from mice at 1, 3, and 7 d post-injury to determine the impact of excisional wounding (EW) independent of burn injury on the systemic inflammatory response
This was evidenced by lower systemic levels of: 1) keratinocyte-derived chemokine (KC) at d 1 post-injury; 2) tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein (MCP)-1 at d 3 post-injury, and; 3) Tissue growth factor (TGF)-β at d 7 post-injury
Summary
Complications induced by burn injury include immunosuppression, sepsis, and delayed wound healing. Immune/ inflammatory cells have an integral function in wound healing beyond their role in inflammation and host defense, as they are essential to the regulation of the wound-healing process through the secretion of signaling molecules, such as cytokines, chemokines, and growth factors [4,5,6]. While the role of inflammatory cells in wound healing is well established, evidence for both positive and negative effects has been suggested. In this regard, recent investigations support the paradigm that robust inflammation, such as that associated with burn injury, may be detrimental to wound closure [9]
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