Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality

Guo, Qi; Song, Weidong; Li, Haiyan; Li, Ming; Chen, Xiaoke; Liu, Hui; Peng, Hong-lin; Yu, Hai-Qiong; Liu, Nian; Lü, Zhong-dong; Liu, Liang; Zhao, Qing-zhou; Jiang, Mei

doi:10.1186/s12931-020-01457-2

Cited by 11 publications

(13 citation statements)

References 33 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several previous preclinical and clinical studies have also demonstrated that hypoxia, both acute and chronic, induce upregulation of intracellular CIRP expression and that acute hypoxia result in release of eCIRP to the extracellular space and circulation (12,13,24). Also, in line with our results, pre-pandemic studies in sepsis and community acquired pneumonia, found that elevated eCIRP levels were prognostic for developing a severe disease or lethal outcome (16,17).…”

Section: Discussionsupporting

confidence: 90%

“…When first described serum levels of eCIRP were undetectable in healthy volunteers, while increased in patients with hemorrhagic shock admitted to the intensive care unit (ICU) (12). Later, serum eCIRP levels have been associated with severe disease and poor prognosis in patients with sepsis, community-acquired pneumonia, and acute pancreatitis (16)(17)(18)(19). Extracellular cold-inducible RNA-binding protein knock out mice (eCIRP-/-) are protected against inflammatory disease (15,20), and neutralizing antibodies against eCIRP are shown to attenuate inflammation and improve survival in animal models of hemorrhagic shock, sepsis, and hepatic ischemia (12,21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19

et al. 2022

View full text Add to dashboard Cite

Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.AimTo investigate if the concentration of extracellular CIRP (eCIRP) in serum associates with respiratory failure and lung involvement by chest computed tomography (CT) in COVID-19.MethodsHerein we report a prospective observational study of patients with COVID-19 included at two University Hospitals in Sweden between April 2020 and May 2021. Serum from hospitalized patients in Örebro (N=97) were used to assess the association between eCIRP and the level of respiratory support and its correlation with pulmonary involvement on chest CT and inflammatory biomarkers. A cohort of hospitalized and non-hospitalized patients from Umeå (N=78) was used as an external validation cohort. The severity of disease was defined according to the highest degree of respiratory support; mild disease (no oxygen), non-severe hypoxemia (conventional oxygen or high-flow nasal oxygen, HFNO <50% FiO2), and severe hypoxemia (HFNO ≥50% FiO2, mechanical ventilation). Unadjusted and adjusted linear regression was used to evaluate peak eCIRP day 0-4 in respect to severity, age, sex, Charlson comorbidity score, symptom duration, and BMI.ResultsPeak eCIRP concentrations were higher in patients with severe hypoxemia and were independently associated with the degree of respiratory support in both cohorts (Örebro; p=0.01, Umeå; p<0.01). The degree of pulmonary involvement measured by CT correlated with eCIRP, rs=0.30, p<0.01 (n=97).ConclusionHigh serum levels of eCIRP are associated with acute respiratory failure in COVID-19. Experimental studies are needed to determine if treatments targeting eCIRP reduces the risk of acute respiratory failure in COVID-19.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19

et al. 2022

View full text Add to dashboard Cite

show abstract

“…e most obvious increase is in children [20]. Studies have also shown [21] that SAA has a certain e indicators such as MLD and double lung V20 in the radiotherapy plan have been widely used in clinical treatment plan evaluation. Since most studies mainly analyze the dose and volume parameters of the irradiated lung tissue from the perspective of radiation physics, it has certain guiding significance.…”

Section: Discussionmentioning

confidence: 99%

Serum MMP-9 and SAA in the Diagnosis of Severe Pneumonia Caused by Radiotherapy of Esophageal Cancer

Zhou

Liu

2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. To explore the relationship and diagnostic value of serum MMP-9 and SAA in severe pneumonia (sCAP) caused by radiotherapy of esophageal cancer. Methods. A total of 144 esophageal cancer patients who underwent radiotherapy in our hospital from April 2016 to February 2018 were collected. Among them, 58 patients without radiation pneumonitis (RP) were in the control group, 49 patients with grade 1∼2 RP were in the radiation group, and 37 patients with sCAP were in the severe group. The levels of serum MMP-9 and SAA in every group of patients were detected. The ROC curve was used to determine the diagnostic value of serum MMP-9 and SAA in the diagnosis of RP and sCAP. The correlation between serum MMP-9 and SAA and the patient’s lung function indexes was analyzed, and the logistic single-factor and multivariate analyses were performed to analyze the factors of sCAP in esophageal cancer radiotherapy. Results. PaO2, FVC, and FEV1 decreased in RP and sCAP, and PaCO2, white blood cells, serum MMP-9, and SAA levels increased ( P < 0.05 ); serum MMP-9 and SAA were negatively correlated with lung function ( P < 0.05 ); the AUC of serum MMP-9 and SAA in RP was 0.833 and 0.823, respectively, and the AUC of the two combined diagnosis of RP was 0.919. The AUC of serum MMP-9 and SAA in sCAP was 0.809 and 0.797, respectively, and the AUC of both combined diagnosis of sCAP was 0.873; logistics multivariate analysis found that serum MMP-9, serum SAA, double lung V5, and V20 were independent risk factors for sCAP caused by radiotherapy for esophageal cancer ( P < 0.05 ). Conclusion. Serum MMP-9 and SAA increase in RP and sCAP and are negatively correlated with lung function in patients with pneumonia. They are independent risk factors for severe pneumonia caused by radiotherapy of esophageal cancer and have good diagnostic value.

show abstract

“…There might be another, yet undefined connection between exRNA and the systemic cytokine storm, hemorrhage, and sepsis that are the major causes of death in COVID-19 patients. This potential connection is based on the role of "coldinducible-RNA binding protein" (CIRP) and its relevance for community-acquired pneumonia, whose severity is related to microbial pathogenicity and virus load (Guo et al, 2020). As a typical DAMP, nuclear CIRP is liberated by macrophages and other cells upon stress and promotes inflammatory responses (cytokine release) via the TLR4-myeloid differentiation factor 2 complex, also causing endothelial dysfunction (Qiang et al, 2013; Figure 1).…”

Section: Perspectives and Hypotheses: Possible Contributions Of Exrnamentioning

confidence: 99%

Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection

Preissner

Fischer

Deindl³

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Upon vascular injury, tissue damage, ischemia, or microbial infection, intracellular material such as nucleic acids and histones is liberated and comes into contact with the vessel wall and circulating blood cells. Such “Danger-associated molecular patterns” (DAMPs) may thus have an enduring influence on the inflammatory defense process that involves leukocyte recruitment and wound healing reactions. While different species of extracellular RNA (exRNA), including microRNAs and long non-coding RNAs, have been implicated to influence inflammatory processes at different levels, recent in vitro and in vivo work has demonstrated a major impact of ribosomal exRNA as a prominent DAMP on various steps of leukocyte recruitment within the innate immune response. This includes the induction of vascular hyper-permeability and vasogenic edema by exRNA via the activation of the “vascular endothelial growth factor” (VEGF) receptor-2 system, as well as the recruitment of leukocytes to the inflamed endothelium, the M1-type polarization of inflammatory macrophages, or the role of exRNA as a pro-thrombotic cofactor to promote thrombosis. Beyond sterile inflammation, exRNA also augments the docking of bacteria to host cells and the subsequent microbial invasion. Moreover, upon vessel occlusion and ischemia, the shear stress-induced release of exRNA initiates arteriogenesis (i.e., formation of natural vessel bypasses) in a multistep process that resembles leukocyte recruitment. Although exRNA can be counteracted for by natural circulating RNase1, under the conditions mentioned, only the administration of exogenous, thermostable, non-toxic RNase1 provides an effective and safe therapeutic regimen for treating the damaging activities of exRNA. It remains to be investigated whether exRNA may also influence viral infections (including COVID-19), e.g., by supporting the interaction of host cells with viral particles and their subsequent invasion. In fact, as a consequence of the viral infection cycle, massive amounts of exRNA are liberated, which can provoke further tissue damage and enhance virus dissemination. Whether the application of RNase1 in this scenario may help to limit the extent of viral infections like COVID-19 and impact on leukocyte recruitment and emigration steps in immune defense in order to limit the extent of associated cardiovascular diseases remains to be studied.

show abstract

Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality

Cited by 11 publications

References 33 publications

Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19

Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19

Serum MMP-9 and SAA in the Diagnosis of Severe Pneumonia Caused by Radiotherapy of Esophageal Cancer

Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection

Contact Info

Product

Resources

About