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Special Issue "Mechanism and Modulation in Sepsis 2.0"

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

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 4825

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Dr. Waldemar Kanczkowski

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Guest Editor

Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Dresden, Germany
Interests: hypothalamus-pituitary-adrenal gland function and dysfunction during sepsis; sepsis and septic shock; tissue-specific vascular biology; pattern recognition receptors; new forms of regulated cell death
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Dear Colleagues,

Sepsis remains associated with a significant morbidity and mortality. The importance of organ injury was recognized in this process and is now included in the diagnostic criteria for sepsis in the most recent sepsis conference (Sepsis-3 conference), replacing the concept of sepsis as mere “systemic inflammatory diseases”. Thus, it is critical to understand the mechanism of organ injury in sepsis, thereby developing approaches to attenuate it. This Special Issue focuses on studies deciphering the mechanism and modulation of organ injury in sepsis, hoping to lead to the improvement of outcome of sepsis.

Dr. Waldemar Kanczkowski
Guest Editor

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Keywords

sepsis
organ injury
pathophysiology
sepsis modulation
outcome

Published Papers (3 papers)

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13 pages, 1632 KiB

Open AccessArticle

Oncostatin M Receptor Type II Knockout Mitigates Inflammation and Improves Survival from Sepsis in Mice

and

Biomedicines 2023, 11(2), 483; https://doi.org/10.3390/biomedicines11020483 - 08 Feb 2023

Cited by 1 | Viewed by 1137

Abstract

Sepsis remains one of the leading causes of death worldwide. Oncostatin M (OSM), an interleukin (IL)-6 family cytokine, can be found at high levels in septic patients. However, little is known about its role in sepsis. This study aimed to determine if the genetic knockout of OSM receptor (OSMR) type II signaling would improve survival in a murine model of sepsis. Aged (>50 weeks) OSMR type II knockout (KO) mice and wild-type (WT) littermates received an intraperitoneal injection of fecal slurry (FS) or vehicle. The KO mice had better survival 48 h after the injection of FS than the WT mice (p = 0.005). Eighteen hours post-FS injection, the KO mice had reduced peritoneal, serum, and tissue cytokine levels (including IL-1β, IL-6, TNFα, KG/GRO, and IL-10) compared to the WT mice (p < 0.001 for all). Flow cytometry revealed decreased recruitment of CD11b⁺ F4/80⁺ Ly6c^high+ macrophages in the peritoneum of KO mice compared to WT mice (34 ± 6 vs. 4 ± 3%, P_Int = 0.005). Isolated peritoneal macrophages from aged KO mice had better live E. coli killing capacity than those from WT mice (p < 0.001). Peritoneal lavage revealed greater bacterial counts in KO mice than in WT mice (KO: 305 ± 22 vs. 116 ± 6 CFU (×10⁹)/mL; p < 0.001). In summary, deficiency in OSMR type II receptor signaling provided a survival benefit in the progression of sepsis. This coincided with reduced serum levels of pro-inflammatory (IL-1β, TNFα, and KC/GRO) and anti-inflammatory markers (IL-10), increased bacterial killing ability of macrophages, and reduced macrophage infiltration into to site of infection. Full article

(This article belongs to the Special Issue Mechanism and Modulation in Sepsis 2.0)

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20 pages, 20074 KiB

Open AccessArticle

Effect of Celecoxib and Infliximab against Multiple Organ Damage Induced by Sepsis in Rats: A Comparative Study

Shaymaa Ramzy Senousy

Mahmoud El-Daly

Ahmed R. N. Ibrahim

Mohamed Montaser A. Khalifa

and

Al-Shaimaa F. Ahmed

Biomedicines 2022, 10(7), 1613; https://doi.org/10.3390/biomedicines10071613 - 06 Jul 2022

Cited by 4 | Viewed by 1533

Abstract

In cases of sepsis, the immune system responds with an uncontrolled release of proinflammatory cytokines and reactive oxygen species. The lungs, kidneys, and liver are among the early impacted organs during sepsis and are a direct cause of mortality. The aim of this study was to compare the effects of infliximab (IFX) and celecoxib (CLX) on septic rats that went through a cecal ligation and puncture (CLP) surgery to induce sepsis. This study included four groups: sham, CLP (untreated), and CLP-treated with CLX or IFX. The administration of “low dose” CLX or IFX was performed after 2 h following the induction of sepsis. Twenty-four hours following the induction of sepsis, the rats were sacrificed and blood samples were collected to evaluate kidney, liver, and lung injuries. MDA and NOx content, in addition to SOD activity and GSH levels, were evaluated in the tissue homogenates of each group. Tissue samples were also investigated histopathologically. In a separate experiment, the same groups were employed to evaluate the survival of septic rats in a 7-day observation period. The results of this study showed that treatment with either CLX or IFX ameliorated the three organs’ damage compared to septic-untreated rats, decreased oxidative stress, enhanced the antioxidant defense, and reduced serum cytokines. As a result, a higher survival rate resulted: 62.5% and 37.5% after the administration of CLX and IFX, respectively, compared to 0% in the CLP group after 7 days. No significant differences were observed between the two agents in all measured parameters. Histopathological examination confirmed the observed results. In conclusion, CLX and IFX ameliorated lung, kidney, and liver injuries associated with sepsis through anti-inflammatory and antioxidant actions, which correlated to the increase in survival observed with both of them. Full article

(This article belongs to the Special Issue Mechanism and Modulation in Sepsis 2.0)

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20 pages, 18510 KiB

Open AccessSystematic Review

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

Emőke Henrietta Kovács

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Biomedicines 2022, 10(9), 2194; https://doi.org/10.3390/biomedicines10092194 - 05 Sep 2022

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Abstract

Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54–1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44–0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25–2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67–2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31–1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63–1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission. Full article

(This article belongs to the Special Issue Mechanism and Modulation in Sepsis 2.0)

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