Circulating LIGHT (TNFSF14) and Interleukin-18 Levels in Sepsis-Induced Multi-Organ Injuries

Abstract

Objective The cytokines, LIGHT (TNFSF14) and Interleukin-18 (IL-18), are two important therapeutic targets due to their central roles in the function of activated T cells and inflammatory injury. LIGHT was recently shown to play a major role in COVID19 induced acute respiratory distress syndrome (ARDS), reducing mortality and hospital stay. This study aims to investigate the associations of LIGHT and IL-18 with non-COVID19 related ARDS, acute hypoxic respiratory failure (AHRF) or acute kidney injury (AKI), secondary to viral or bacterial sepsis. Research Design and Methods A cohort of 280 subjects diagnosed with sepsis, including 91 cases with sepsis triggered by viral infections, were investigated in this study and compared to healthy controls. Serum LIGHT, IL-18, and 59 other biomarkers (cytokines, chemokines and acute-phase reactants) were measured and associated with symptom severity. Results ARDS was observed in 36% of the patients, with 29% of the total patient cohort developing multi-organ failure (failure of two or more organs). We observed significantly increased LIGHT level (>2SD above mean of healthy subjects) in both bacterial sepsis patients (P=1.80E-05) and patients with sepsis from viral infections (P=1.78E-03). In bacterial sepsis, increased LIGHT level associated with ARDS, AKI and higher Apache III scores, findings also supported by correlations of LIGHT with other biomarkers of organ failures, suggesting LIGHT may be an inflammatory driver. IL-18 levels were highly variable across individuals, and consistently correlated with Apache III scores, mortality, and AKI, in both bacterial and viral sepsis. Conclusions For the first time, we demonstrate independent effects of LIGHT and IL-18 in septic organ failures. LIGHT levels are significantly elevated in non-COVID19 sepsis patients with ARDS and/or multi-organ failures suggesting that anti-LIGHT therapy may be effective therapy in a subset of patients with sepsis. Given the large variance of plasma IL-18 among septic subjects, targeting this pathway raises opportunities that require a precision application.

A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease

“…To identify the NAFLD patients showing impaired performance in each parameter measured by these tests, we applied the mean ± 2 SD criterion [21,[27][28][29], calculating the mean and SD of the value for each parameter for the control group and adding or subtracting twice the SD to this mean to obtain a cutoff (see Table 2). This cutoff was applied to assess which parameters show impaired performance in each patient.…”

“…Patients whose parameter score was within the range of the mean ± 2 SD were classified as without impairment and those falling outside this range were classified as having impaired performance for this parameter. This criterion has been previously used to identify patients with impaired performance in psychometric tests [21] and also to identify data outside the normal range in many other types of studies [27][28][29]. We used these data to design a new method to classify patients as with MCI or without MCI (NMCI) by developing a new score, as described in the results section.…”

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“…Research has revealed distinct differences in clinical characteristics, molecular mechanisms and treatment responses among the ARDS subtypes 10 . Clinical studies have shown that patients with sepsis‐induced ARDS phenotype are more severely ill than non‐sepsis‐related ARDS patients, have poorer recovery from lung injury, lower extubation success rates, higher short‐term mortality, and poor long‐term prognosis 11,12 . Due to the complex and diverse mechanism of exogenous lung injury in sepsis, the exact mechanism is not fully understood.…”

TNF superfamily control of tissue remodeling and fibrosis

“…A recent study by Qu et al. suggests that LIGHT plays a role in viral and bacterial sepsis induced acute respiratory distress syndrome (ARDS) ( 53 ). From a cohort of 280 patients, in the bacterial sepsis cases (n=189), significantly elevated LIGHT was associated with ARDS, higher Apache III scores, acute kidney injury (AKI), and acute hypoxic respiratory failure (AHRF).…”