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Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.

ABSTRACT: A systemic inflammatory response is observed in patients undergoing hemorrhagic shock and sepsis. Here we report increased levels of cold-inducible RNA-binding protein (CIRP) in the blood of individuals admitted to the surgical intensive care unit with hemorrhagic shock. In animal models of hemorrhage and sepsis, CIRP is upregulated in the heart and liver and released into the circulation. In macrophages under hypoxic stress, CIRP translocates from the nucleus to the cytosol and is released. Recombinant CIRP stimulates the release of tumor necrosis factor-? (TNF-?) and HMGB1 from macrophages and induces inflammatory responses and causes tissue injury when injected in vivo. Hemorrhage-induced TNF-? and HMGB1 release and lethality were reduced in CIRP-deficient mice. Blockade of CIRP using antisera to CIRP attenuated inflammatory cytokine release and mortality after hemorrhage and sepsis. The activity of extracellular CIRP is mediated through the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex. Surface plasmon resonance analysis indicated that CIRP binds to the TLR4-MD2 complex, as well as to TLR4 and MD2 individually. In particular, human CIRP amino acid residues 106-125 bind to MD2 with high affinity. Thus, CIRP is a damage-associated molecular pattern molecule that promotes inflammatory responses in shock and sepsis.

SUBMITTER: Qiang X

PROVIDER: S-EPMC3826915 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.

Qiang Xiaoling X Yang Weng-Lang WL Wu Rongqian R Zhou Mian M Jacob Asha A Dong Weifeng W Kuncewitch Michael M Ji Youxin Y Yang Huan H Wang Haichao H Fujita Jun J Nicastro Jeffrey J Coppa Gene F GF Tracey Kevin J KJ Wang Ping P

Nature medicine 20131006 11

A systemic inflammatory response is observed in patients undergoing hemorrhagic shock and sepsis. Here we report increased levels of cold-inducible RNA-binding protein (CIRP) in the blood of individuals admitted to the surgical intensive care unit with hemorrhagic shock. In animal models of hemorrhage and sepsis, CIRP is upregulated in the heart and liver and released into the circulation. In macrophages under hypoxic stress, CIRP translocates from the nucleus to the cytosol and is released. Rec ...[more]

PMID: 24097189

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Project description:Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%).Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA.The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37-30.17) ng/mL and 1.68 (1.41-13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage.An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis.

Project description:BackgroundAcute ischemic stroke (AIS) is the leading cause of morbidity and mortality among cerebrovascular diseases. While animal studies have suggested a correlation between cold-inducible RNA-binding protein (CIRP) serum levels and the severity and prognosis of cerebral infarction, there has been a lack of research exploring this association in humans with cerebral infarction.Materials and methodsA total of 148 patients diagnosed with AIS within 7 days from symptom onset were included in this study. Comprehensive information regarding the patients' basic demographics, medical history, clinical parameters, the severity of cerebral infarction, and serum CIRP levels was collected. Follow-up data were obtained through telephonic interviews or by reviewing clinical notes for 3 months after the patients were discharged to assess the functional outcomes of treatment.ResultsThe findings of this study demonstrated a significant increase in serum CIRP levels during the early stages of AIS, followed by a gradual decline after 3 days. Significant differences were observed in the serum CIRP levels between the 1-day group and the 4-7 day group (P < 0.0047), as well as between the 2-3 day group and the 4-7 day group (P < 0.0006). Moreover, a significant positive correlation was observed between the serum CIRP levels and the severity of cerebral infarction. Higher serum CIRP levels were associated with more severe National Institutes of Health Stroke Scale scores (P < 0.05) and larger cerebral infarction volumes (P < 0.05). Furthermore, patients with higher serum CIRP levels exhibited poorer modified Rankin scale scores (P < 0.05). These findings indicate that serum CIRP serves as an essential pro-inflammatory mediator and a valuable biomarker for assessing brain injury in patients with AIS.ConclusionThe findings of this study suggest an elevation in serum CIRP levels among patients with AIS. These levels are positively correlated with the severity of AIS and serve as indicators of a poor prognosis. Therefore, CIRP could serve as a target for early clinical intervention while managing AIS, and further research should explore serum CIRP levels as prognostic indicators in AIS.

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Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.

Publications

Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.

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