Burns are among the most devastating injuries, representing a major global public health crisis [1], [2], [3], especially in middle- and low-income countries [4]. Globally, over 11 million people are hospitalized for burns annually according to the World Health Organization. Hypertrophic scars (HTS) are a fibroproliferative response, occurring in up to 70% of patients after burn injuries [5]. These abnormal scars are erythematous, thickened, and raised masses of scar tissue generally confined to the wound boundary, which causes patients significant pruritus, dysesthesias, contractures as well as emotional discomfort [1], [6]. There is data in animal models and in vitro to suggest that circulating monocytes and their chemokine receptors are important in the development of HTS after burn injury [7], [8]. However, the range of perturbations in monocyte pathophysiology and their cytokine and chemokine signaling pathways which may contribute to the development of HTS in human patients after burn injury is unclear, and as a result, effective treatment of HTS is suboptimal.

Cytokines are known to have a significant role in wound healing at all stages, however most notably during inflammation [9]. Cytokines are responsible for pushing the wound healing process into the next stage, involved in regulation of normal healing and the dysregulation seen in HTS [10]. B-cell attracting chemokine (BCA)-1, or CXCL13, has not been researched in burns at varying levels, however has been shown to upregulate collagen type I mRNA expression in osteoarthritic patients [11]. BCA-1 attracts pro-inflammatory cytokines [12], and has been found in the blood monocytes of severely burned patients as M2c monocytes [13]. In previous study, we described the role of stromal cell-derived factor 1 and its receptor CXCR4 (SDF-1/CXCR4) signaling in the formation of HTS following burn injury. This chemokine pathway appears to be upregulated in the serum and CD14+ CXCR4+ expressing peripheral blood mononuclear cells (PBMCs) [14]; however, this study was conducted during the remodeling phase of wound healing when patients were rehabilitating from burn injury and the number of patients studied did not allow correlations to be made for the severity of burn injury.

Chemokines recruit blood-borne cells such as monocytes, which function as pro- or anti-inflammatory cells to the site of injury [15], [16]. Circulating monocytes are recruited by chemokines into wound sites, differentiate into various subtypes of macrophages in the tissue, and play an indispensable role in wound healing [17], [18]. Monocytes express chemokine receptors, which bind their ligands to carry out specific immune responses, playing roles in both normal healing and fibrotic scarring. Although chemokines are involved during all stages of wound healing [19], little research has been done in the burn population. We investigated changes in circulating monocytes and their subpopulations, chemokine receptor expressions, as well as chemokine and cytokine levels in the blood of burn patients with varying severity of injury at multiple time points post-burn injury, to understand their potential roles in scarring after burn injury to provide potential therapeutic opportunities.