BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.
Amniocentesis ; Amniotic Fluid ; Area Under Curve ; Biomarkers ; Blood Proteins ; Cervix Uteri ; Complement System Proteins ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; Interleukins ; Labor Stage, First ; Outcome Assessment (Health Care) ; Plasma ; Pregnancy ; Progesterone ; Retrospective Studies ; Risk Factors ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinases

To observe the changes in serum interleukin-22 (IL-22) level and its correlation with other clinical indexes in patients with essential hypertension and hypertensive renal damage, and to investigate its effects and clinical significance.
 Methods: A total of 97 essential hypertension (EH) patients and 40 healthy control were enrolled in this study. The EH patients were divided into a simple hypertension (SH) group (n=45) and a hypertensive renal damage (HRD) group (n=52) according to 24 h urinary protein (24 h-UPRO) level. Basic clinical data were collected; serum IL-22 level was detected by enzyme-linked immunosorbent assay (ELISA); the proportion of Th22 cells in peripheral blood was evaluated by flow cytometry (FCM); and serum high sensitivity C-reactive protein (hs-CRP) concentration was measured by immune turbidimetry. Correlation analysis was applied between serum IL-22 level and other indexes.
 Results: Serum IL-22 level and Th22 cell proportion in patients with hypertension were significantly higher than those in the healthy controls (all P<0.01). Compared with the SH group, serum IL-22 level and Th22 cell proportion were significantly elevated in the HRD group (P<0.01, P<0.05, respectively). Bivariate linear correlation analysis revealed that serum IL-22 level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hsCRP (r=0.367, P<0.01; r=0.402, P<0.01; r=0.329, P<0.05); there was also a positive correlation between serum IL-22 concentration and Th22 cell proportion (r=0.478, P<0.01) in the SH group. Serum IL-22 level was positively correlated with 24 h-UPRO level (r=0.318, P<0.05) in the HRD group.
 Conclusion: Serum IL-22 level and peripheral blood Th22 cells are significantly increased in the HRD group compared with the SH group. Serum IL-22 level is closely correlated with extent of hypertensive renal damage, indicating that serum IL-22 level may involve in the pathogenesis of hypertensive renal damage.
Blood Pressure ; C-Reactive Protein ; Humans ; Hypertension ; Interleukins

Blood Donors ; Genotype ; Hepacivirus ; Hepatitis C ; Humans ; Interferons ; Interleukins ; Prevalence

INTRODUCTION: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive. METHODS: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented. RESULTS: Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%. CONCLUSION Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.
Acute Kidney Injury ; blood ; complications ; Adult ; Alleles ; Blood Donors ; Female ; Genotype ; Hepatitis C ; epidemiology ; Humans ; Interleukins ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prevalence ; Renal Dialysis ; Singapore ; epidemiology ; Substance Abuse, Intravenous ; blood ; epidemiology ; Young Adult

BACKGROUND: Chronic inflammation has been linked to insulin resistance and type 2 diabetes mellitus (T2DM). High-fat diet (HFD)-derived fatty acid is associated with the activation of chronic inflammation in T2DM. PF-04620110, which is currently in phase 1 clinical trials as a selective acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) inhibitor, is a potent anti-diabetic agent that may be important for the regulation of chronic inflammation in T2DM. However, the mechanisms by which PF-04620110 regulates fatty acid-induced chronic inflammation remain unclear. METHODS: PF-04620110 was used in vitro and in vivo. DGAT1-targeting gRNAs were used for deletion of mouse DGAT1 via CRISPR ribonucleoprotein (RNP) system. The activation of NLRP3 inflammasome was measured by immunoblot or cytokine analysis in vitro and in vivo. RESULTS: Here we show that PF-04620110 suppressed fatty acid-induced nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome activation in macrophages. In contrast, PF-04620110 did not change the activation of the NLR family, CARD-domain-containing 4 (NLRC4), or the absent in melanoma 2 (AIM2) inflammasomes. Moreover, PF-04620110 inhibited K⁺ efflux and the NLRP3 inflammasome complex formation, which are required for NLRP3 inflammasome activation. PF-04620110 reduced the production of interleukin 1β (IL-1β) and IL-18 and blood glucose levels in the plasma of mice fed HFD. Furthermore, genetic inhibition of DGAT1 suppressed fatty acid-induced NLRP3 inflammasome activation. CONCLUSION: Our results suggest that PF-04620110 suppresses fatty acid-induced NLRP3 inflammasome activation.
Animals ; Blood Glucose ; Clinical Trials, Phase I as Topic ; Clustered Regularly Interspaced Short Palindromic Repeats ; Diabetes Mellitus, Type 2 ; Diacylglycerol O-Acyltransferase ; Diet, High-Fat ; Fatty Acids ; Humans ; In Vitro Techniques ; Inflammasomes ; Inflammation ; Insulin Resistance ; Interleukin-18 ; Interleukins ; Macrophages ; Melanoma ; Mice ; Plasma ; Ribonucleoproteins ; RNA, Guide

BACKGROUND: Several factors, including clinical manifestations and laboratory data, have been used to evaluate the disease activity of Sjögren's syndrome (SS). We investigated saliva indicators of disease activity in primary SS patients. METHODS: We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF-α), and rheumatoid factor (RF)-IgA levels in saliva samples were measured using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was measured with an automatic ESR analyzer. The t-test and Pearson correlation test were used. RESULTS: IL-6 level was higher in primary SS patients than in normal controls (14.23±14.77 vs 9.87±7.32, P=0.012), but there were no significant differences in IL-17A, TNF-α, and RF-IgA levels. In primary SS patients, IL-6 level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248, P=0.017, respectively), and TNF-α level correlated weakly with IgG level (r=0.231, P=0.024). CONCLUSIONS: IL-6 may play a role in SS pathogenesis. Saliva IL-6 might be an indicator of disease activity in primary SS patients.
Blood Sedimentation ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoassay ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Interleukin-17 ; Interleukin-6 ; Interleukins ; Nephelometry and Turbidimetry ; Rheumatoid Factor ; Saliva ; Tumor Necrosis Factor-alpha

PURPOSE: The aim of this study was to evaluate the relationships between cytokine and chemokine levels and the clinical severity of Mycoplasma pneumoniae pneumonia. METHODS: A retrospective analysis of clinical and laboratory parameters were performed. Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-18, interferon-γ-inducible protein-10 (IP-10), macrophage inflammatory protein-1β, and tumor necrosis factor-α were measured. The severity of patients' clinical course and radiologic findings were also assessed. RESULTS: Seventy-two patients (35 males and 37 females) with a median age of 3.9 years (range, 1–16 years) were enrolled. Patients with lobar pneumonia (n=29) had significantly higher C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-18 values than those with broncho-interstitial pneumonia (n=43). However, the cytokine and chemokine values did not differ between the group that was treated with corticosteroids (n=31) and the one that was not (n=41). The CRP, ESR, lactate dehydrogenase (LDH), IL-18, and IP-10 values showed positive correlations with fever duration prior to admission. The CRP and ESR values were positively correlated with IL-18, and LDH, with IP-10 levels. CONCLUSIONS: CRP, ESR, LDH, IL-18, and IP-10 values were associated with the severity of the disease, manifesting lobar pneumonia or prolonged fever duration prior to admission.
Adrenal Cortex Hormones ; Blood Sedimentation ; C-Reactive Protein ; Chemokines ; Child ; Cytokines ; Fever ; Humans ; Interleukin-10 ; Interleukin-18 ; Interleukin-8 ; Interleukins ; L-Lactate Dehydrogenase ; Macrophages ; Male ; Mycoplasma pneumoniae ; Mycoplasma ; Necrosis ; Pneumonia ; Pneumonia, Mycoplasma ; Retrospective Studies

BACKGROUND: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. METHODS: Beagle dogs (n=8; weight, 6.5–9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. RESULTS: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin (IL)-1β levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. CONCLUSION: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.
Animals ; Anticoagulants ; Blood Platelets ; Dogs ; Extracorporeal Membrane Oxygenation* ; Hemorrhage ; Heparin ; Interleukin-10 ; Interleukins ; Mesylates* ; Partial Thromboplastin Time ; Thrombelastography ; Tumor Necrosis Factor-alpha

The present study investigated the effects of interleukin (IL)-4 on dopamine (DA) neurons in the substantia nigra (SN) in vivo of lipopolysaccharide (LPS)-treated rat. Tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral DA neurons at 3 and 7 day post-LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 day and remained elevated at 7 day post-LPS. IL-4 immunoreactivity was detected exclusively in microglia. IL-4 neutralizing antibody (NA) significantly increased survival of DA neurons in LPS-treated SN in vivo by inhibiting microglial activation and production of proinflammatory mediator such as IL-1β as assessed by immunihistochemical, RT-PCR and ELISA analysis, respectively. Accompanying neuroprotection are IL-4NA effects on decreased disruption of blood-brain barrier and astrocytes. The present data suggest that endogenously expressed IL-4 from reactive microglia may be involved in the neuropathological processes of degeneration of DA neurons occurring in Parkinson's disease.
Animals ; Antibodies, Neutralizing ; Astrocytes ; Blood-Brain Barrier ; Dopamine* ; Dopaminergic Neurons* ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; Interleukin-4* ; Interleukins ; Lipopolysaccharides ; Microglia ; Neurons ; Neuroprotection ; Parkinson Disease ; Rats ; Substantia Nigra* ; Tyrosine 3-Monooxygenase

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor (TNF)-α, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of TNF-α, interleukin (IL)-1β, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.
Animals ; Apoptosis* ; Blood Urea Nitrogen ; Caspase 3 ; Constriction ; Creatinine ; Cytokines ; Fibrosis ; In Situ Nick-End Labeling ; Interleukin-6 ; Interleukins ; Ischemia ; Kidney ; Macrophages ; Mice ; Muscle Cells ; Necrosis ; Plaque, Atherosclerotic ; Receptors, Angiotensin ; Reperfusion Injury* ; Tumor Necrosis Factor-alpha ; Up-Regulation