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The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis.

ABSTRACT: Growth differentiation factor 15 (GDF15) is involved in the occurrence and development of many diseases, and there are few studies on its relationship with sepsis. This article aims to explore the clinical value of GDF15 in sepsis and to preliminarily explore its prospective regulatory effect on macrophage inflammation and its functions. We recruited 320 subjects (132 cases in sepsis group, 93 cases in nonsepsis group, and 95 cases in control group), then detected the serum GDF15 levels and laboratory indicators, and further investigated the correlation between GDF15 and laboratory indicators, and also analyzed the clinical value of GDF15 in sepsis diagnosis, severity assessment, and prognosis. In vitro, we used LPS to stimulate THP-1 and RAW264.7 cells to establish the inflammatory model, and detected the expression of GDF15 in the culture medium and cells under the inflammatory state. After that, we added GDF15 recombinant protein (rGDF15) pretreatment to explore its prospective regulatory effect on macrophage inflammation and its functions. The results showed that the serum GDF15 levels were significantly increased in the sepsis group, which was correlated with laboratory indexes of organ damage, coagulation indexes, inflammatory factors, and SOFA score. GDF15 also has a high AUC in the diagnosis of sepsis, which can be further improved by combining with other indicators. The dynamic monitoring of GDF15 levels can play an important role in the judgment and prognosis of sepsis. In the inflammatory state, the expression of intracellular and extracellular GDF15 increased. GDF15 can reduce the levels of cytokines, inhibit M1 polarization induced by LPS, and promote M2 polarization. Moreover, GDF15 also enhances the phagocytosis and bactericidal function of macrophages. Finally, we observed a decreased level of the phosphorylation of JAK1/STAT3 signaling pathway and the nuclear translocation of NF-κB p65 with the pretreatment of rGDF15. In summary, our study found that GDF15 has good clinical application value in sepsis and plays a protective role in the development of sepsis by regulating the functions of macrophages and inhibiting the activation of JAK1/STAT3 pathway and nuclear translocation of NF-κB p65.

SUBMITTER: Li H

PROVIDER: S-EPMC8456026 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionWe explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN).MethodsWe enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made.ResultsOn the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence.ConclusionsBesides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients.Trial registrationClinicalTrial.gov identifier NCT01333657.

Project description:BackgroundNeonatal sepsis remains one of the leading causes of mortality and morbidity in developing countries. With a dearth of data on neonatal sepsis in our country, this study was conducted to determine the incidence of clinical neonatal sepsis and evaluate the clinical, bacteriological, and antimicrobial susceptibility profile of organisms. Material and Methods. A prospective cross-sectional study was conducted in the Neonatal Unit of the National Hospital from 1st January to 31st December 2016. All neonates admitted with suspected clinical sepsis were included. Sepsis screens and cultures were sent under aseptic conditions. Data was analyzed using STATA™ version 12. Clinical features and neonatal and maternal risk factors were analyzed using chi-squared test. Bacteriological profile was analyzed with descriptive statistics.ResultsDuring the study period, incidence of culture positive neonatal sepsis was 19 per 1000 admissions with a blood culture positivity rate of 14%. 54.5% had culture-positive early-onset sepsis (EOS). Prematurity (p = 0.012), APGAR < 6 (p = 0.018), low birth weight (p < 0.001), and maternal intrapartum antibiotics (p = 0.031) significantly increased risk for culture-positive EOS. Prematurity (p < 0.001), low birth weight (p = 0.001), and parental nutrition (p = 0.007) were significantly associated with increased risk of culture-positive late-onset sepsis. A positive screen had sensitivity of 81.8% and negative predictive value of 87.7%. Gram-negative organisms were most commonly isolated (64.6%). Coagulase-negative Staphylococci (31%) were the commonest isolate followed by Klebsiella pneumoniae (27%) and Acinetobacter (18.8%). Ninety percent of Acinetobacter were carbapenem resistant. Gram-negative sepsis had mortality of 88.9%.ConclusionPreterm, low birth weight, low APGAR scores, intrapartum antibiotics, and parental nutrition were significantly associated with neonatal sepsis. Coagulase-negative Staphylococci, Klebsiella pneumoniae, and Acinetobacter were the principal causative organisms. Gram-negative organisms had high resistance to commonly used antibiotics.

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The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis.

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