Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1498974
This article is part of the Research Topic Exploring Immunomodulation to Balance Maladaptive Inflammation and Restore Tissue Homeostasis View all articles

Time-Dependent Variation in Immunoparalysis Biomarkers Among Patients with Sepsis and Critical Illness

Provisionally accepted
Abigail Samuelsen Abigail Samuelsen 1Erik Lehman Erik Lehman 2Parker Burrows Parker Burrows 1Anthony S Bonavia Anthony S Bonavia 1*
  • 1 Penn State Milton S. Hershey Medical Center, Hershey, United States
  • 2 College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, United States

The final, formatted version of the article will be published soon.

    Immunoparalysis is a state of immune dysfunction characterized by a marked reduction in the immune system's responsiveness, often observed following severe infections, trauma, or critical illness. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness. We compared ex vivo-stimulated cytokine release from whole blood of critically ill patients to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients. Results showed that while mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more pronounced in septic patients. Ex vivo stimulation of blood from septic patients revealed significant increases in TNF and IL-6 production over time.However, interferon-gamma production varied depending on the ex vivo stimulant used and, after normalization of cytokine concentrations to lymphocyte counts, it did not show significant recovery over time from illness onset. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers. These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional 'sepsis' versus 'non-sepsis' classifications in critically ill patients. Additionally, they provide further evidence of a potential window for targeted immunotherapy in the first weeks of critical illness.

    Keywords: Sepsis, Critical Illness, immune monitoring, immunodeficiency, Human leukocyte antigen-DR, Lymphocyte Count

    Received: 19 Sep 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Samuelsen, Lehman, Burrows 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: Anthony S Bonavia, Penn State Milton S. Hershey Medical Center, Hershey, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.