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A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
The diagnostic and immunomodulatory role of IL-37 in pediatric sepsis
Jin Ma1, Yanling Zhang2, Changrui Sun1
1Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Insights
Elevated interleukin-37 (IL-37) shows promise as a diagnostic biomarker for pediatric sepsis. This study demonstrates IL-37
Area of Science:
- Immunology
- Pediatric Critical Care
- Inflammation Research
Background:
- Sepsis is a life-threatening condition caused by a dysregulated inflammatory response to infection.
- The specific role of interleukin-37 (IL-37) in pediatric sepsis requires further investigation.
Purpose of the Study:
- To evaluate IL-37 as a diagnostic biomarker in pediatric sepsis.
- To investigate the immunomodulatory effects of IL-37 in pediatric sepsis.
Main Methods:
- Serum IL-37 levels were measured in two independent pediatric sepsis cohorts.
- Immunomodulatory effects were studied using a murine sepsis model and ex vivo experiments with peripheral blood mononuclear cells (PBMCs).
Main Results:
- Higher serum IL-37 levels were observed in pediatric sepsis patients compared to controls.
- IL-37 administration in mice reduced inflammation and improved survival.
- IL-37 neutralization in PBMCs altered immune cell populations.
Conclusions:
- Elevated IL-37 is a potential diagnostic biomarker for pediatric sepsis.
- IL-37 modulates hyperinflammation and immune cell differentiation, suggesting it as a therapeutic target.
Objective:
Sepsis arises from a dysregulated host inflammatory response to infection. The levels and pathogenic role of interleukin-37 (IL-37) in pediatric sepsis remain to be fully elucidated.
Methods:
Serum IL-37 concentrations were measured in two independent cohorts of pediatric patients with sepsis from Chongqing (discovery cohort, n=40) and Sichuan (validation cohort, n=105). The immunomodulatory effects of IL-37 were systematically investigated through: 1) a murine sepsis model (cecal ligation and puncture), and 2) ex vivo experiments using peripheral blood mononuclear cells (PBMCs) from patients under standardized culture conditions.
Results:
Admission serum IL-37 levels were significantly higher in pediatric patients with sepsis compared to non-septic patients and healthy controls. To assess its diagnostic potential, ROC curve analyses were performed, yielding areas under the curve (AUC) of 0.76 [P<0.0001; 95% confidence interval (95% CI), 0.66 - 0.85] and 0.77 [P<0.0001; 95% CI, 0.71 - 0.84] from the two medical centers. In septic mice, therapeutic administration of recombinant IL-37 significantly attenuated systemic inflammation (reduced IL-6, CXCL-1, CCL-2; increased IL-10), decreased the proportion of M1 macrophages without altering total macrophage counts in peritoneal lavage fluids (PLF), and improved survival rates. In vitro, IL-37 neutralization with a specific antibody in septic PBMCs increased the percentages of CD4+ T cells and NKT cells.
Conclusion:
This study identifies elevated IL-37 as a potential diagnostic biomarker for pediatric sepsis and demonstrates its role in modulating hyperinflammation and immune cell differentiation. IL-37 represents a promising therapeutic target for pediatric sepsis.
