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Biomedicines
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Sepsis and Systemic Inflammation: Mechanisms and Therapeutic Innovations
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Sepsis and Systemic Inflammation: Mechanisms and Therapeutic Innovations

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 2146

Editor

Prof. Dr. Christian Lehmann

E-Mail Website
Guest Editor
Department of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
Interests: cannabinoids; infection; sepsis and its early indications; intravital imaging microcirculation; septic shock stroke
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue explores the complex interplay between sepsis, systemic inflammation, and associated organ dysfunction, where we aim to showcase cutting-edge research on pathophysiological mechanisms and translational innovations. Contributions are welcome to delve into early inflammatory markers, microcirculatory dysfunction assessed via intravital imaging, and immune dysregulation in sepsis. This Special Issue aims to highlight novel therapeutic strategies, including interventions targeting microvascular perfusion and immunomodulation, alongside advancements in pharmacologic agents, biomarkers, and precision medicine approaches. Integrating animal models and clinical studies, we hope that this Special Issue bridges the gaps between basic science and clinical applications, aiming to redefine diagnostic criteria and therapeutic paradigms for sepsis, septic shock, and systemic inflammation.

Prof. Dr. Christian Lehmann
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sepsis
  • systemic inflammation
  • microcirculation
  • intravital imaging
  • immune dysregulation
  • septic shock
  • therapeutic innovations

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Published Papers (2 papers)

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Research

17 pages, 2766 KB  
Article
HIF-1α Promotes Macrophage Extracellular Trap Formation and Exacerbates Acute Lung Injury in Neonatal Sepsis
by Huiling Zhang, Wei Huang, Xinlong Dai, Jundi Zheng, Xinyao Jiang, Yutao Yang, Hanhui Zhong and Guang Yang
Biomedicines 2026, 14(5), 1145; https://doi.org/10.3390/biomedicines14051145 - 18 May 2026
Viewed by 469
Abstract
Background: Acute lung injury (ALI) is a major contributor to mortality in neonatal sepsis, yet the mechanisms underlying early lung damage remain incompletely understood. Although extracellular traps (ETs) have been implicated in inflammatory injury, the cellular origin and regulatory pathways of ET [...] Read more.
Background: Acute lung injury (ALI) is a major contributor to mortality in neonatal sepsis, yet the mechanisms underlying early lung damage remain incompletely understood. Although extracellular traps (ETs) have been implicated in inflammatory injury, the cellular origin and regulatory pathways of ET formation in neonatal sepsis remain unclear. This study aimed to determine the source of ETs and to investigate the role of hypoxia-inducible factor-1α (HIF-1α) in regulating macrophage extracellular traps (METs) formation and lung injury. Methods: Neonatal sepsis was induced in mice by intraperitoneal injection of cecal slurry. METs formation was assessed by immunofluorescence staining, Western blotting, and extracellular DNA quantification. Selective depletion of macrophages or neutrophils was performed to determine the cellular source of ETs. In vitro experiments were conducted using macrophages stimulated with lipopolysaccharide or phorbol 12-myristate 13-acetate. RNA sequencing analysis and pharmacological inhibition were used to examine the roles of HIF-1α, glycolysis, and enolase 2 (ENO2) in METs formation, lung injury, and survival outcomes. Results: We identify macrophages as a predominant source of ETs in the lung and demonstrate that METs contribute to lung injury in neonatal sepsis. Depletion of macrophages or pharmacological inhibition of METs formation markedly attenuated lung injury and improved survival in neonatal sepsis mice. Mechanistically, we suggest that HIF-1α promotes METs formation by driving glycolysis in macrophages. Furthermore, this process appears to involve the upregulation of key glycolytic enzymes, including ENO2, potentially facilitating METs release. In turn, METs are implicated in enhancing macrophage inflammatory activation, which could exacerbate lung injury. Importantly, pharmacological targeting of HIF-1α pathways reduces METs formation, attenuates lung inflammation, and improves survival outcomes. Conclusions: These findings suggest a role for HIF-1α in regulating METs formation and support that targeting this pathway could represent a potential therapeutic strategy for neonatal sepsis-associated acute lung injury. Full article
(This article belongs to the Special Issue Sepsis and Systemic Inflammation: Mechanisms and Therapeutic Innovations)
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14 pages, 784 KB  
Article
Predictive Value of Platelet-Based Indexes for Mortality in Sepsis
by Alice Nicoleta Drăgoescu, Adina Turcu-Stiolica, Marian Valentin Zorilă, Bogdan Silviu Ungureanu, Petru Octavian Drăgoescu and Andreea Doriana Stănculescu
Biomedicines 2026, 14(1), 211; https://doi.org/10.3390/biomedicines14010211 - 19 Jan 2026
Cited by 2 | Viewed by 1100
Abstract
Background: Even though there have been improvements in antimicrobial and supportive therapies, sepsis and septic shock are still major causes of death in intensive care units. Early prognostic stratification is very important for helping doctors make decisions. Platelet-derived indices may provide useful, low-cost [...] Read more.
Background: Even though there have been improvements in antimicrobial and supportive therapies, sepsis and septic shock are still major causes of death in intensive care units. Early prognostic stratification is very important for helping doctors make decisions. Platelet-derived indices may provide useful, low-cost indicators that signify both inflammatory activation and coagulation irregularities. This study looked at how well different platelet-based ratios could predict death in the hospital from sepsis. Materials and Methods: We performed a prospective observational study spanning one year in a tertiary ICU, enrolling 114 adult patients diagnosed with sepsis or septic shock. Upon admission, four platelet-related biomarkers were measured: the C-reactive protein-to-platelet ratio (CPR), the platelet-to-lymphocyte ratio (PLR), the platelet-to-white blood cell ratio (PWR), and the platelet-to-creatinine ratio (PCR). Logistic regression models and receiver operating characteristic (ROC) analyses were employed to assess predictive accuracy. Results: Compared to survivors, non-survivors (n = 39) had much higher CRP levels and CPR values, alongside lower platelet and lymphocyte counts. The CPR index showed the best ability in differentiating between non-survivors and survivors (AUC 0.757), with a best cutoff of 0.886. In simplified multivariate models, CPR was still an independent predictor of death in the hospital (OR 1.98; 95% CI 1.22–3.21), whereas PLR and PWR were not. PCR showed a non-significant trend toward lower values in not survivors. Conclusions: CPR is a strong and clinically viable predictor of early mortality in sepsis, outperforming other platelet-based indices. Derived from routine laboratory parameters, CPR serves as a valuable adjunct for initial risk stratification in the ICU. To further confirm its prognostic role and incorporation into current scoring systems, large-scale multicenter studies with longitudinal measurements are warranted to validate its prognostic utility and integration into existing scoring systems. Full article
(This article belongs to the Special Issue Sepsis and Systemic Inflammation: Mechanisms and Therapeutic Innovations)
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