Severity of thermal burn injury is associated with systemic neutrophil activation

Abstract

Burn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far. Serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Serum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI). Taken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.

Figure 1

Elevated neutrophil-derived factors and C3a in burn sera. Systemic levels of (A) MPO, (B) CitH3, (C) NE, and (D) C3a were quantified in sera of burn victims (n = 8–19) and healthy controls (n = 4–6) up to 4 weeks post injury. Data were compared by mixed effects analysis and Sidak’s multiple comparisons post hoc test. Data are presented as means ± s.e.m. Asterisks indicate p values < .05.

Figure 2

Immune cell counts up to 4 weeks post injury. Patient data in relation to established in-hospital reference standards (n = 1–31). Data are presented as means ± s.e.m.

Figure 3

Increased levels of neutrophil-derived factors and C3a in higher degree burns. Serum concentrations of (A) MPO, (B) CitH3, (C) NE, and (D) C3a in 3rd degree burn victims (n = 7–15) compared to lower degree burns (n = 1–6). Data are presented as means ± s.e.m. * indicates p values < .05.

Figure 4

Serum concentrations of neutrophil-derived factors in low and high ABSI scores. ABSI scores were determined on admission day and categorized into low (≤ 8, n = 19) and high (≥ 9, n = 13) values. Serum concentrations of MPO, CitH3, NE, and C3a of the first 7 days post admission were compared. Data were statistically evaluated by Mann–Whitney test.