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

2021 ◽  
Author(s):  
Hui-Qi Qu ◽  
Jingchun Qu ◽  
Thomas Dunn ◽  
James Snyder ◽  
Todd A. Miano ◽  
...  
Keyword(s):  
Viral Infections ◽  
Kidney Injury ◽  
Light Therapy ◽  
Light Level ◽  
Interleukin 18 ◽  
Bacterial Sepsis ◽  
Activated T Cells ◽  
Acute Phase Reactants ◽  
Apache Iii ◽  
Organ Failures

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.

scholarly journals Pharmacokinetics and Safety of Intravenous Cidofovir for Life-Threatening Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

2015 ◽  
Vol 59 (7) ◽  
pp. 3718-3725 ◽  
Author(s):  
Amy E. Caruso Brown ◽  
Mindy N. Cohen ◽  
Suhong Tong ◽  
Rebecca S. Braverman ◽  
James F. Rooney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Half Life ◽  
Viral Infections ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Cell Transplant ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Life Threatening

ABSTRACTChildren undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.

MO1012ACUTE KIDNEY INJURY IN PREMATURE INFANTS EXPOSED TO PERINATAL HYPOXIA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Iuliia Kyslova ◽  
Tetiana Savrun ◽  
Olga Yablon ◽  
Oleksandr Mazulov ◽  
Natalia Nazarchuk
Keyword(s):  
Renal Artery ◽  
Cystatin C ◽  
Premature Infants ◽  
Flow Rate ◽  
Gestational Age ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Renal Tubules ◽  
Perinatal Hypoxia ◽  
Interleukin 18

Abstract Background and Aims Features of nephrogenesis and functional state of the kidneys of premature infants makes them extremely vulnerable to the damaging effects of hypoxia. The imperfection of traditional methods of diagnosis and non-specific clinical manifestations of ischemic nephropathy in premature infants requires the study of new informative diagnostic tests that would indicate the development of a pathological process in the renal tissue. The aim is to early diagnose acute kidney injury in preterm infants exposed to perinatal hypoxia, based on the study of renal blood flow and laboratory markers - cystatin C in serum, lipocalin and interleukin-18 in urine. Method We examined premature infants exposed to perinatal hypoxia and had signs of injury of kidney depending on gestational age: 65 infants with gestational age <32 weeks and 50 infants with gestational age > 32 weeks. The group of comparison included 25 premature newborns who were born without hypoxia and without signs of kidney injury. Blood and urine samples were obtained at 2-4 days of life. Ultrasound examination of the kidneys was performed at 3-5 days of life. Results The level of CysC in the serum of infants with gestational age <32 and> 32 weeks significantly exceeded this level in infants of the group of comparison (in infants with gestational age <32 weeks -2.50 [2.14; 3.26] ng/ml, in infants with gestational age> 32 weeks - 1.89 (1.49; 2.45] ng/ml), p <0.01. The value of NGAL in the urine of infants with gestational age <32 weeks - Me 96.03 [38,6; 131.23] ng/ml UCr and of infants with gestational age > 32 weeks - Me 75.10 [31,24; 126.6] ng/ml UCr against Me 25.9 [8.24; 44.64] ng/mg UCr in infants of the group of comparison (p <0.01). IL-18 in the urine of infants with gestational age <32 weeks and > 32 weeks was significantly higher than that in infants of the group of comparison (Me 27.98 [25.49; 29.51] pg/mg UCr, Me 22.0 [19.6; 25.63] pg/mg UCr, and 17.41 [13.96; 18.78] pg/mg UCr, respectively, p <0.01). According to the results of duplex scanning, the maximum systolic flow rate in the trunk of the renal artery (Vmax) in infants with gestational age <32 weeks (35.62 ± 3.2 cm/s) was lower than in infants of the group of comparison (p <0.05). Decreased IR less than 0.6 in 19 (29.3 ± 5.6%) infants with gestational age <32 weeks and in 12 (24.0 ± 6.4%) infants with gestational age > 32 weeks indicates vasodilation and, possibly arteriovenous shunting. The pulsation index in infants with gestational age <32 weeks and > 32 weeks (0.88 ± 0.1 and 0.98 ± 0.1) was significantly lower than in the group of comparison (p <0.05). Conclusion Early (2-4 days of life) and significant (p<0.01) increase in serum cystatin C, interleukin-18 and lipocalin associated with neutrophil gelatinase in the urine indicate endogenous renal dysfunction, damage to the proximal renal tubules in premature infants who were exposed to perinatal hypoxia. Significant decrease in the maximum systolic flow rate in the trunk of the renal artery and pulsation index (p<0.05) in premature infants who underwent perinatal hypoxia indicate a significant impact of circulatory disorders on the formation of hypoxic nephropathy.

Abstract 17113: Secondary Infections Are Common in Patients Hospitalized for COVID-19 and Are Associated With Severe Outcomes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Elizabeth R Anderson ◽  
Tariq Azam ◽  
Husam Shadid ◽  
Michael Pan ◽  
Hanna Berlin ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Viral Infections ◽  
Clinical Laboratory ◽  
Secondary Infection ◽  
Kidney Injury ◽  
Outcome Data ◽  
Hospitalized Patients ◽  
Secondary Infections ◽  
Life Threatening ◽  
The Mean

Background: Secondary infections occur in 10-15% of critically ill sepsis patients. Anecdotal reports suggest secondary infections are common in coronavirus disease 2019 (COVID-19), however data are lacking. We examine the rate of secondary infections in hospitalized patients with COVID-19 and its impact on the cytokine surge and in-hospital outcomes. Methods: The Michigan Medicine Covid-19 Cohort (M2C2) is an ongoing prospective observational study in which detailed clinical, laboratory and outcome data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without respiratory symptoms were not included in this cohort. We define secondary infections as physician-diagnosed and treated bacterial or viral infections secondary to SARS-CoV-2. Results: Of 553 COVID-19 patients hospitalized at Michigan Medicine, 191 (34.5%) developed a secondary infection during hospitalization. The mean age of patients with a secondary infection was 60 years, 61.3% were male compared to 58.8 years, 53.5% male in patients with no secondary infection. Bacterial pneumonia, including ventilator-associated pneumonia, was the most prevalent secondary infection among hospitalized patients (78.5%). Other secondary infections included urosepsis (14.1%), bacteremia (16.8%), and 17.3% of patients developed other types of infections such as shingles and clostridium difficile. 25.8% of patients without secondary infections received antibiotics during their admission compared to 47.1% of patients with secondary infections. Multiple secondary infections (>1) occurred in 43 (8.2%) of patients. Patients with secondary infections were more likely to develop acute kidney injury (78.0% vs. 38.3%, p<0.0001), acute respiratory distress syndrome (78.0% vs. 22.3%, p<0.0001), and death (26.2% vs. 10.2%, p<0.0001) during their hospitalization compared to patients without secondary infections. Conclusions: Secondary infections are common in hospitalized patients with COVID-19 and are associated with life-threatening complications and high mortality. This study suggests that secondary infection prevention may be especially important in COVID-19 patients.

Hepatitis-Associated Glomerulonephritis

2019 ◽  
pp. 389-396
Author(s):  
Julie Belliere ◽  
Stanislas Faguer ◽  
Nassim Kamar
Keyword(s):  
Membranoproliferative Glomerulonephritis ◽  
Hepatitis A ◽  
Viral Infections ◽  
Kidney Injury ◽  
Hepatitis E ◽  
Common Type ◽  
Viral Clearance ◽  
Antiviral Therapies ◽  
Immune Phenomena ◽  
Membranous Nephritis

Viral hepatitis can be associated with extrahepatic manifestations, including kidney injury, mainly glomerulonephritis (GN). The physiopathology of GN is of particular interest because some immune responses, triggered by viral infections, can harm the glomerulus, either via deposition of immune complexes, auto-immune phenomena, or through cytopathogenic effects. This chapter describes the epidemiology of hepatitis A-, B-, C-, and E-associated GN; the clinical and biological presentations; the histological patterns; and management regimens. Few cases of hepatitis A- or hepatitis E-associated GN have been reported. Cryoglobulinemic membranoproliferative glomerulonephritis is the most common type of GN diagnosed in patients infected by the hepatitis C virus. Patients infected by hepatitis B mainly develop membranous nephritis. Viral clearance using antiviral therapies, when available, is necessary to improve kidney outcomes.

scholarly journals GB Virus C E2 Inhibits PD-1-Mediated T Cell Signaling Dysfunction during Chronic Viral Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 62
Author(s):  
Nirjal Bhattarai ◽  
Jennifer L. Welch ◽  
Jinhua Xiang ◽  
Muthu Saravanan Manoharan ◽  
Jeffrey A. Martinson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infections ◽  
Activated T Cells ◽  
E2 Protein ◽  
Gb Virus C ◽  
Cell Dysfunction ◽  
Chronic Viral Infections ◽  
T Cell Dysfunction ◽  
Virus C

Background: Program death receptor 1 (PD-1) is a co-inhibitory receptor that is upregulated and contributes to T cell dysfunction (exhaustion) during chronic viral infections, including HIV and HCV. GB virus C (GBV-C) is a persistent human virus, and co-infection is associated with reduced immune activation and improved clinical outcomes in HIV- and Ebola-infected individuals. Methods: PD-1 levels were measured by flow cytometry on CD38+ T cells from 45 HIV-infected individuals, 20 of whom were co-infected with GBV-C. Jurkat cell lines that stably express GBV-C E2 protein and vector control were used to purify total cellular RNA before, and 24 h following, activation using anti-CD3/CD28 treatment. Gene expression was analyzed by RNA-seq and qRT-PCR. Results: HIV-infected individuals with GBV-C viremia had reduced PD-1 expression on activated CD4+ and CD8+ T cells compared to HIV-infected GBV-C negative individuals. GBV-C particles and GBV-C E2 protein each inhibited PD-1 expression on T cells in vitro. Consistent with this, GBV-C E2 reduced gene expression of PD-1, and its ligand PD-L1, in both resting and activated T cells. GBV-C E2 regulated transcription of the PD-1 signaling pathway and T cell activation associated genes, without downregulation of the interferon-stimulated and innate immunity-related genes needed to resolve viral infections. Conclusions: Our current understanding of chronic RNA virus infections is that upregulation of PD-1 with T cell exhaustion is critical for viral persistence. However, these data demonstrate that GBV-C infection reduced PD-1 expression on activated T cells during HIV infection, and that the GBV-C E2 protein inhibits PD-1 signaling in T cells. This may preserve T cell function and contribute to the lack of immune deficiency in people with chronic GBV-C infection. Understanding the mechanisms by which GBV-C E2 alters PD-1 signaling may aid in the development of novel immunomodulatory therapeutics to prevent T cell dysfunction (exhaustion) during chronic viral infections.

scholarly journals Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients

2015 ◽  
Vol 114 (3) ◽  
pp. 460-468 ◽  
Author(s):  
S. Nisula ◽  
R. Yang ◽  
M. Poukkanen ◽  
S.T. Vaara ◽  
K.M. Kaukonen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Predictive Value ◽  
Kidney Injury ◽  
Adult Patients ◽  
Interleukin 18

scholarly journals Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis—A Prospective Cohort Study

2016 ◽  
Vol 34 (01) ◽  
pp. 01-07 ◽  
Author(s):  
Lena Klein ◽  
Julia Winter ◽  
Isabella Schmeh ◽  
Britta Gröndahl ◽  
Stephan Gehring ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Viral Infections ◽  
Late Onset ◽  
Bacterial Sepsis

T cell-T cell activation in multiple sclerosis

1997 ◽  
Vol 3 (4) ◽  
pp. 238-242 ◽  
Author(s):  
JW Lindsey ◽  
RH Kerman ◽  
JS Wolinsky
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Viral Infections ◽  
Activated T Cells ◽  
In Vitro Proliferation

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

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