Immunoparalysis is mediated by a dysfunctional IL-10/IL-12 axis in severe burn injury

Autor: Wesley H Stepp, Madison Malfitano, Clayton Long, Robert Maile, Bruce A Cairns
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Immunology. 198:63.20-63.20
ISSN: 1550-6606
0022-1767
Popis: In the past year alone, burn injuries accounted for greater than 500,000 medical encounters in the United States. Few molecular markers exist that can detail the extent of burn severity or predict outcomes in burn patients. The identification of biomarkers that can accurately predict patients who are at a higher risk for in-hospital complications and would improve patient outcomes. In this study, we identified means to objectively quantify the degree of a patient’s burn injury and developed a gene-expression profile that identifies the degree of immune compromise in patients following significant burn trauma. In a prospectively collected cohort of 54 burn patients, we identified that the amount of cell-free DNA in a patient’s plasma significantly correlates with the degree of burn severity (as determined by % total body surface area affected, %TBSA) (R2=0.4256; p15% TBSA) for gene expression analysis of key immunoregulatory molecules. When compared to uninjured, healthy control subjects (N=13), patients with low-moderate injuries (N=33) had 10-fold upregulation in IL-10 expression (p=0.0004), while patients with severe burn injuries (N=18) had a more pronounced upregulation in IL-10 gene expression (25.85-fold increase, p=0.0029). Conversely, IL-12 gene expression remained constant in low-moderate burn patients but was significantly decreased in patients with severe burn injuries. These data suggest that severe burn injury generates a profoundly dysfunctional immune response that may prove a significant challenge to recovery.
Databáze: OpenAIRE