ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1520848
Functional Immune Profiling of Hyper-and Hypo-inflammatory Subphenotypes of Critical Illness: A Secondary Analysis
Provisionally accepted
- 1Division of Pediatric Critical Care Medicine, Department of Pediatrics, Penn State University, Hershey, United States
- 2Department of Molecular and Precision Medicine, Penn State University College of Medicine, Hershey, PA, United States
- 3Division of Pediatric Hematology and Oncology, Department of Pediatrics, The Pennsylvania State University, Hershey, Pennsylvania, United States
- 4Department of Anesthesiology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, United States
- 5Department of Public Health Sciences, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, United States
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Functional Immune Profiling of Hyper-and Hypo-inflammatory Subphenotypes of Critical Illness: A Secondary Analysis Subjects were divided into hypo-inflammatory (42 patients) and hyper-inflammatory (18 patients) subtypes using a previously validated parsimonious model based on concentrations of IL-6, TNFR1 and bicarbonate. The hyper-and hypo-inflammatory clusters demonstrated a near four-fold difference in 30-day mortality (44.4% vs 11.9%, p=0.0046). Following 4h of ex vivo stimulation with LPS, TNF production was lower in the hyper-inflammatory group as compared with the hypo-inflammatory group (p=0.0159). Ex vivo phorbol 12-myristate 13-acetate (PMA)stimulated IFN-g production (4h) by whole blood did not differ between groups.These data further validate the use of IL-6, TNFR1 and bicarbonate to discern inflammatory sub-groups of patients with critical illness. They also confirm the observation that the presence of the hyper-inflammatory subphenotype is often accompanied by a compensatory anti-inflammatory response syndrome. Future investigations should focus on prospective validation of this panel for prognostic enrichment of clinical research studies.
Keywords: Sepsis, biomarker, phenotype, Cytokines, Critical Illness, Humans
Received: 31 Oct 2024; Accepted: 18 Apr 2025.
Copyright: © 2025 Halstead, McKeone, Samuelsen, Zhou and Bonavia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: E. Scott Halstead, Division of Pediatric Critical Care Medicine, Department of Pediatrics, Penn State University, Hershey, United States
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