What is it about?
Sepsis is the most common cause of death on intensive care units and one of the few diseases challenging healthcare systems worldwide. The disease is defined as a dysregulated immune response towards invading pathogens, such as bacteria. In the traditional view, at least in early stages, the disease is characterized by an overreaction of the host's own immune cells against a pathogen, which ends up damaging the host itself. Based on this concept, many studies have attempted to block the overzealous immune reaction of early sepsis, such as using Toll-like receptor blockers that inhibit the recognition of pathogen parts. However, these treatments failed to improve disease outcomes. This study found that early sepsis appears to be more heterogeneous than previously thought with only a subset of patients displaying features of a strong inflammation even when sampling within 1 day of sepsis diagnosis. This ongoing inflammation as measured in patient blood samples with minimal manipulation correlated with the samples' response to Toll-like receptor blockers.
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Why is it important?
The large heterogeniety of early sepsis phenotypes questions the general use of anti-inflammatory drugs even in very early phases of sepsis, that are still often described as hyperinflammation or "cytokine storm". This does not seem to reflect the status in a majority of sepsis cases. However, those samples that showed signs of hyperinflammation also tended to react to TLR-blocker treatment. Thus, proper patient selection, for example via ex vivo models like the one developed in this study, may enable targeted therapy of receptive patients.
Perspectives
Due to the fast disease progression and multifactioral diagnosis, early sepsis data sets of a proper size for statistical analysis are relatively rare, and generating one posed one of the main challenges of this project. I'm glad that the cooperation between microbiology and anesthesiology / intensive care team brought this sizeable dataset of clinical data and matched lab results. The whole blood ex vivo model shines in its minimal sample manipulation and thus conceptually presents an unfiltered view into the situation inside the patient at that time, which was exciting, although, given the still high mortality of the disease, also scary at times.
Dr. med. Willem Buys
Johns Hopkins University
Read the Original
This page is a summary of: Substantial heterogeneity of inflammatory cytokine production and its inhibition by a triple cocktail of toll-like receptor blockers in early sepsis, Frontiers in Immunology, October 2023, Frontiers,
DOI: 10.3389/fimmu.2023.1277033.
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