Clinical Importance of a Cytokine Network in Major Burns

Abstract

Major burns elicit an acute inflammatory response including various inflammatory cytokines. Cytokines play mutual interacting roles in inflammatory diseases. There is little evidence of the clinical significance of the cytokine network in patients with major burns. This study aimed to investigate the clinical significance of the cytokine network in patients with major burn. This prospective observational study comprising 38 patients with major burns (total body surface area (%TBSA) ≥ 20%) and 12 healthy controls was conducted from April 2014 to December 2016. Blood samples were collected from patients at six points: day 1, day 2, days 3-5, 1 week, 2 weeks and 1 month after the burn injury. Inflammatory cytokines (IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, MCP-1, TNF-α) and anti-inflammatory cytokines (IL-4, IL-10) were measured. Twenty-eight-day mortality, %TBSA, prognostic burn index (PBI) and SOFA and APACHE II scores were evaluated. Hierarchical clustering analysis and network visualization showed one cluster and network, respectively. Both were formed by four cytokines including IL-6, IL-8, IL-10 and MCP-1 on days 1 and 2, suggesting the presence of a cytokine network in the early hospital phase. Each cytokine showed significant associations with the SOFA score within 5 days and 1 month after burn injury. Cox regression analysis highlighting days 1 and 2 showed significant correlation of IL-6, IL-8 and IL-10 with 28-day mortality. We showed a cytokine network and its relation with prognosis and injury severity on days 1 and 2 and suggest that this cytokine network may play a role in major burns.

IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome

“…Elevated levels of proinflammatory cytokines are associated with the clinical manifestations of CRS ( 15 , 16 ). For example, several cytokines in the sera of sepsis or burn patients are correlated with patient prognosis and disease severity ( 17 , 18 ). To explore the importance of the cytokine network in the pathogenesis of CRS, we reconstituted and reanalyzed the cytokine profiles of sera from CRS patients ( 17 , 18 ).…”

“…For example, several cytokines in the sera of sepsis or burn patients are correlated with patient prognosis and disease severity ( 17 , 18 ). To explore the importance of the cytokine network in the pathogenesis of CRS, we reconstituted and reanalyzed the cytokine profiles of sera from CRS patients ( 17 , 18 ). A total of 91 patients with CRS associated with sepsis, acute respiratory distress syndrome (ARDS), or burns were enrolled in this study.…”

Burn-Induced Coagulopathies: a Comprehensive Review

“…Cytokine derangements are more severe in adult patients when compared with children and this heightened immunoinflammatory response has been suggested as a contributor to the increased morbidity and mortality observed in adults ( 87 ). Matsuura et al examined a cytokine network including monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, and IL-10 and showed that cytokine derangements in burn patients with > 20% TBSA compared with healthy controls were correlated with burn injury severity and prognosis ( 90 ). When compared with non-burn trauma patients, patients with severe burns were found to have higher levels of IL-6 and IL-8 as early as 24 h after injury ( 91 ).…”

“…The inflammatory and hypermetabolic state that develops after burn injury persists following the acute phase ( 90 , 101 ). Nonsurvivors have significantly higher plasma levels of IL-1, IL-6, IL-10, IL-12, and TNF-α at 1 week from burn injury when compared with survivors ( 85 ).…”

Current and Emerging Topical Scar Mitigation Therapies for Craniofacial Burn Wound Healing

“…Larger burns are also correlated with the systemic release of inflammatory cytokines, including interleukin 6 (IL-6), IL-8, IL-10, and monocyte chemoattractant protein 1 (MCP-1) (Bergquist et al, 2019). In a study of 38 patients with major burns, Hiroshi et al demonstrated that these four systemic inflammatory markers correlated with Sequential Organ Failure Assessment (SOFA) scores, while IL-6, IL-8, and IL-10 correlated with 28-day mortality (Matsuura et al, 2019). Finally, disruption of the skin barrier increases the susceptibility of the patient to infections caused by bacteria, fungus, and viruses.…”