Inflammatory Cytokine Profile Research Articles

β2-microglobulin alters the profiles of inflammatory cytokines and of matrix metalloprotease in macrophages derived from the osteoarthritic synovium

Several studies have implicated β2-microglobulin (B2M) in osteoarthritis (OA) pathology. Of the main constituents of synovial tissue, synovial fibroblasts and macrophages, the latter play a pivotal role in inflammation. Although several studies have investigated the effects of B2M on synovial fibroblasts, few have examined the impact on synovial macrophages. Here, we investigated the effect of B2M on the expression profiles of inflammatory cytokines and matrix metalloproteases (MMPs) in synovial macrophages. Synovial macrophages were isolated from the osteoarthritic synovium using an anti-CD14 anti- body and magnetic isolation system. Synovial macrophages were stimulated with B2M for 6 and 24 h. Following stimulation, cell surface marker (CD80, CD163, CD206), cytokine [interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α)] and matrix metalloprotease (MMP; MMP-9 and MMP-13) genes were evaluated by real-time PCR. Additionally, cytokine concentrations in cell culture supernatant were determined using enzyme-linked immunosorbent assay (ELISA). B2M significantly increased CD80 and decreased CD163 expression. In addition, B2M stimulation increased inflammatory cytokines at both the mRNA and protein levels. While B2M likewise elevated MMP-13 levels, there was no difference in MMP-9 expression between vehicle and B2M-treated cells. B2M increased M1 macrophage marker, inflammatory cytokine, and MMP-13 expression in synovial macrophages. B2M-related activation of synovial macrophages may thus be associated with OA pathology.

Comparison of Th1 and Th17 Inflammatory Cytokine Profiles Between Chronic Plaque and Acute Guttate Psoriasis.

BackgroundThe phenotypic heterogeneity of psoriasis is suspected to reflect differences in its pathogenesis, but not yet completely elucidated. Studies of the Th1 and Th17 cytokines associated with different phenotypes of psoriasis have yielded inconsistent results.ObjectiveTo investigate the tissue expression levels of Th1 and Th17 cytokines among patients with chronic plaque psoriasis, acute guttate psoriasis, and healthy control.MethodsA total of 20 patients with psoriasis (10 with chronic plaque type and 10 with acute guttate type) and 5 healthy controls were enrolled. The tissue mRNA and protein levels of following cytokines were measured: interleukin (IL)-12, IL-2, interferon (IFN)-γ, IL-23, IL-17A, and IL-22.ResultsThe tissue mRNA levels of IL-12, IFN-γ, IL-23, IL-17A, IL-22 and the protein levels of IL-12, IL-2, IFN-γ, IL-17A, IL-22 were significantly increased in the psoriasis patients compared with the healthy controls. In comparisons of the subtypes, the tissue mRNA level of IFN-γ was increased in acute guttate psoriasis, whereas the protein levels of IL-12 and IL-17A were significantly increased in chronic plaque psoriasis. The cytokine ratios of IL-17A/IL-2 and IL-22/IL-2 were significantly higher in chronic plaque psoriasis than in acute guttate psoriasis.ConclusionWe confirmed that the tissue levels of Th1 and Th17 cytokines were increased in psoriasis patients compared with healthy controls. The increased IFN-γ mRNA level in acute guttate psoriasis and increased IL-12 and IL-17A protein levels in chronic plaque psoriasis suggest that an imbalance between Th1 and Th17 cytokines may play a role in the phenotypic transition of psoriasis.

Identifying Unique Inflammatory Cytokine Profiles in Maternal-Fetal Dyads with COVID-19

Dysregulated immunity plays a critical role in determining COVID-19 disease severity. Pregnancy increases the risk for severe morbidity, yet little is known about how this altered immune state influences maternal-fetal immunity. We investigated cytokine responses to SARS-CoV-2 in maternal-fetal dyad pairs.

Advanced Glycation End Products and Inflammatory Cytokine Profiles in Maintenance Hemodialysis Patients After the Ingestion of a Protein-Dense Meal

The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal. CON (n=8; 50±2years; 31±1kg/m2) and MHD patients (n=8; 56±5years; 32±2kg/m2) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-β, total IκBα, and pIκBα). Basal circulating AGEs were 7- to 343-fold higher (P<.001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P<.001). There was a group effect (MHD>CON) for total sRAGEs (P=.02) and endogenous secretory RAGEs (P<.001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD<CON; P<.05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1β and a trend (P<.10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P<.001). In muscle, Toll-like receptor 4 (P=.03), TIR-domain-containing adapter-inducing interferon-β (P=.002), and oligosaccharyltransferase subunit 48 (P=.02) expression was lower in MHD than that in CON, whereas IL6 was higher (P=.01) and IL8 (P=.08) tended to be higher in MHD. Overall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status.

Aberrant hepatic trafficking of gut-derived T cells is not specific to primary sclerosing cholangitis.

The "gut homing" hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut-derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine "the gut homing theory" in patients with PSC with associated inflammatory bowel disease (PSC-IBD) and across multiple inflammatory liver diseases. Expression of MAdCAM-1, CCL25, and E-Cadherin were assessed histologically and using RT-PCR on explanted liver tissue from patients with CLD undergoing OLT and in normal liver. Liver mononuclear cells were isolated from explanted tissue samples and the expression of gut homing integrins and cytokines on hepatic infiltrating gut-derived T cells was assessed using flow cytometry. Hepatic expression of MAdCAM-1, CCL25 and E-Cadherin was up-regulated in all CLDs compared with normal liver. There were no differences between disease groups. Frequencies of α4β7, αEβ7, CCR9, and GPR15 expressing hepatic T cells was increased in PSC-IBD, but also in CLD controls, compared with normal liver. β7 expressing hepatic T cells displayed an increased inflammatory phenotype compared with β7 negative cells, although this inflammatory cytokine profile was present in both the inflamed and normal liver. These findings refute the widely accepted "gut homing" hypothesis as the primary driver of PSC and indicate that aberrant hepatic recruitment of gut-derived T cells is not unique to PSC, but is a panetiological feature of CLD.

Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis.

BackgroundAccumulating evidence has shown the important role of the inflammatory process in the pathophysiology of mental disorders. However, the relative levels of inflammatory markers in patients with panic disorder (PD) have rarely been evaluated. The aim of the present study was to conduct a systematic review to determine the correlation of peripheral C-reactive protein (CRP) and inflammatory cytokine profiles with PD.MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for quantitative research studies published up to July 31, 2021 that measured peripheral levels of CRP and inflammatory cytokines in people with PD compared with controls. Meta-analysis using a random-effects model was performed for the levels of CRP and inflammatory cytokines with data from three or more studies.ResultsFourteen identified studies met the inclusion criteria. In total, 18 cytokines were evaluated. Markers that were reported in more than 3 studies were included in this meta-analysis. The results showed that peripheral levels of CRP, IL-6, IL-2 and TNF-α were significantly higher in PD patients than in healthy controls, while there was no significant difference in peripheral levels of IL-1β, IL-10 and IFN-γ between groups. Notably, the relevant studies involving IL-6, IL-1β, IL-10 and IFN-γ in PD patients were highly heterogeneous. Similar to meta-analyses of other inflammatory factors in mental disorders, our meta-analysis also reflected differences in participant medication use, comorbid anxiety or depression, sampling methods and detection methods. Eight inflammatory cytokines were reported in only one study, and their expression levels were higher, lower, or unchanged compared with those in healthy controls.ConclusionThere is preliminary evidence to suggest a significant inflammatory response in PD patients, but the role of inflammatory markers in PD remains unclear. Studying inflammatory markers in PD will help to clarify the etiology and pathophysiological mechanisms of the disorder.

Дегенеративная болезнь диска у молодых: цитокиновый профиль и факторы ангиогенеза

Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p &lt; 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p &lt; 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p &lt; 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p &lt; 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p &lt; 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p &lt; 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.

MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses

Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-let-7a miRNA in response to Staphylococcus epidermidis Small Colony Variants infection. We also assessed whether the expression levels of inflammatory cytokines associated with the hsa-let-7a are manipulated by the pathogen and the effect of the IFN-γ priming on the expression of hsa-let-7a and the fate of SCVs/WTs in infected macrophages. A striking observation was the downregulation of the let-7a miRNA upon challenge of the THP-1 activated cells with the SCV isolates while no significant changes in expression were noticed after the infection of macrophages with their WT counterparts. Staphylococcus epidermidis WT and SCV strains were found to invade and survive in macrophages. A significant reduction in bacterial load for both phenotypes was observed in macrophages treated with let-7a mimic compared to untreated ones. Survival of WTs was augmented in cells treated with the inhibitor in 4 out of 5 strains as compared to the number of bacteria recovered from non-transfected cells. At the same time, let-7a inhibitor did not influence on the survival of SCVs in macrophages as their number was comparable to number recovered from non-transfected cells. When the ratio of both let-7a cytokine targets was compared, anti-inflammatory IL-10 cytokine was induced by SCVs predominantly, while the macrophage challenge with WTs was characterized by the inflammatory cytokine profile with high IL-6 and low IL-10 production. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines has been expectedly retrieved when macrophages were transfected with let-7a mimic before infection with WT or SCV strains. The results also show that IFN-γ likely regulates the macrophage environment contributing to the inflammatory response and elimination of bacteria from intracellular milieu by augmenting the synthesis of pro-inflammatory cytokines and supressing the anti-inflammatory IL-10. Our work has shown that SCVs have the potential to regulate the let-7a miRNA to balance the pro-inflammatory IL-6 with anti-inflammatory IL-10 and this mechanism is one of the ways in a complex regulatory network adopted by SCVs to promote their survival.

Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers.

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1β, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.

Time to face the proofs: the BCG Moreau vaccine promotes superior inflammatory cytokine profile in vitro when compared with Russia, Pasteur, and Danish strains

ABSTRACT Tuberculosis (TB) has been a major public health problem worldwide, and the Bacillus Calmette–Guérin (BCG) vaccine is the only available vaccine against this disease. The BCG vaccine is no longer a single organism; it consists of diverse strains. The early-shared strains of the BCG vaccine are stronger immunostimulators than the late-shared strains. In this study, we have employed a simple in vitro human model to broadly evaluate the differences among four widely used BCG vaccines during the characterization of strain-specific host immune responses. In general, the BCG Moreau vaccine generated a higher inflammatory cytokine profile and lower TGF-β levels compared with the Russia, Pasteur, and Danish strains in the context of early sensitization with TB; however, no changes were observed in the IL-23 levels between infected and noninfected cultures. Unsurprisingly, the BCG vaccines provided different features, and the variances among those strains may influence the activation of infected host cells, which ultimately leads to distinct protective efficacy to tackle TB.

Omega-3 fatty acids and blood-based biomarkers in Alzheimer’s disease and mild cognitive impairment: A randomized placebo-controlled trial

BackgroundIncreased serum levels of pro-inflammatory biomarkers are consistently associated with cognitive decline. The omega-3 unsaturated fatty acids (n-3 PUFAs) had been linked to slowing cognitive decline due to their potential anti-inflammatory effects. To our knowledge, the different regiments of pure DHA, pure EPA, and their combination on various associated symptoms of dementia, including a mild form of cognitive impairment (MCI) and Alzheimer’s disease (AD), have never been studied. MethodsThis multisite, randomized, double-blind, placebo-controlled trial was conducted at two veteran’s retirement centers and one medical center in central Taiwan between 2013 and 2015. 163 MCI or AD patients were randomly assigned to placebo (n = 40), docosahexaenoic acid (DHA, 0.7 g/day, n = 41), eicosapentaenoic acid (EPA, 1.6 g/day, n = 40), or EPA (0.8 g/day) + DHA (0.35 g/day) (n = 42) group for 24 months. The results were measured as the cognitive and functional abilities, biochemical, and inflammatory cytokines profiles. Chi-square tests, two-sample t-test, ANOVA, and linear mixedeffects models were conducted with p < 0.05. Results131 (80%) participants had completed the trial with all cognitive, functional, and mood status assessments. The statistically significant difference between the placebo and treatment groups was not determined, concerning the changes in cognitive, functional, and mood status scores, the biochemical profiles, and inflammatory cytokines levels. However, EPA was found to reduce the C–C motif ligands 4 (CCL4) level (p < 0.001). Additionally, EPA could reduce the constructional praxis (p < 0.05) and spoken language ability scores (p < 0.01), and DHA also reduced the spoken language ability score (p < 0.05). ConclusionOverall, n-3 PUFAs supplements did not reduce cognitive, functional, and depressive symptom outcomes, but spoken language ability and constructional praxis subitems of ADAS-cog. These findings show that attention to clinical heterogeneity in dementia is crucial when studying nutrients interventions, such as n-3 PUFAs. In addition, with small effect size CCL4 is a better indicator than other inflammatory cytokines for EPA treatment response.

The association of the quality of sleep with proinflammatory cytokine profile in inflammatory bowel disease patients

BackgroundThe role of circadian rhythm abnormalities in patients with inflammatory bowel disease (IBD) remains relatively unknown. The aim of this study was to identify the inflammatory cytokine profile in the IBD patients and its relationship with the quality of sleep.MethodsProspective, single-center observational cohort study was performed. In all enrolled adult IBD patients, the disease activity was assessed using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. To assess the quality of sleep, all patients were asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all enrolled patients, 15 ml venous blood was taken to determine serum inflammatory cytokine levels and perform standard laboratory tests.ResultsFifty-two IBD patients were enrolled in the study: 32 with CD and 20 with UC. The poor sleep was noted in 69.4% of patients with clinically active and in 6.3% of patients with inactive disease. In the group of IBD patients with poor sleep, the significantly higher level of serum IL-6, IL-17, and IL-23 were observed. In IBD patients with exacerbation, the significantly higher level of serum IL-6, IL-17, and IL-23 were recorded.ConclusionsThe relationship between quality of sleep and proinflammatory cytokine profile may show us a predisposition for the development of inflammatory intestinal lesions in IBD patients with sleep disturbances. This knowledge may allow the pharmacological and behavioral therapies of circadian rhythm abnormalities to become new significant targets in IBD patients.

Mapping Pulmonary and Systemic Inflammation in Preschool Aged Children With Cystic Fibrosis

The immune landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. In this work, we used high parameter flow cytometry and inflammatory cytokine profiling to map the local [bronchoalveolar lavage (BAL)] and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and aged-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b+ granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. Inflammatory cells in the BAL from both CF and healthy children expressed higher levels of activation and migration markers relative to their systemic counterparts. This work highlights the utility of multiplex immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood.

Perirenal Fat and Chronic Kidney Disease in Patients With Diabetes.

The burden of chronic kidney disease (CKD) in patients with diabetes is high, and recent studies have highlighted the key role of perirenal fat (PRF) thickness in its pathophysiology (1,2). Indeed, increased PRF thickness has been associated with an unfavorable profile of inflammatory cytokines, atherosclerosis, dyslipidemias, metabolic syndrome, and unfavorable outcomes after nephrectomy (3–11). In this issue of Diabetes , …

SARS‐CoV‐2 neutralizing antibodies decline over one year and patients with severe COVID‐19 pneumonia display a unique cytokine profile

ObjectivesAs coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity. MethodsThis study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups. ResultsPeak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups. ConclusionsThe study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Is there an inflammatory stimulus to human term labour?

Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (PGHS-2, PGDH, OTR and CX43) in all of the tissues at the onset of labour and oxytocin (OT) mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1β and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in prolabour factor mRNA levels suggests that the cytokines may act on the myometrium where we observed changes in transcription factor activation and increases in prolabour gene expression in earlier studies.

Marked up-regulation of anti inflammatory cytokine gene expression in the peripheral blood mononuclear cells of postpartum cows with endometritis

This study was designed to determine the mRNA expression profile of inflammatory and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMC) of endometritic and non-endometritic cows to find out a possible marker for diagnosis of endometritis. Cows (21) including 12 endometritic, and 9 normal (non-endometritic) that did not develop uterine diseases postpartum (pp) were selected. Expression profile (mRNA) of cytokines, viz. IL-1β, TNFα, IL-8 and IL-4 in endometritic cows relative to non-endometritic was studied in PBMC isolated from the blood of the cows collected within 4 to 5 weeks pp. Fold difference (n-fold) in cytokine gene expression in the PBMC of endometritic cows relative to normal was calculated using relative quantification method (2-ΔΔCt). The relative fold change in gene expression for IL-1 was significantly lower in endometritic animals (0.31) than in cows that did not develop endometritis. Significant up-regulation was noted for the proinflammatory cytokine TNFα (9.53 fold and anti-inflammatory cytokine IL-4 (90.09) in cows suffering from endometritis relative to nonendometritic cows. Up-regulation of chemokine IL-8 gene (6.25 fold; was also observed in endometritic compared to non-endometritic cows. Highest and significant up-regulation of mRNA expression for IL-4 followed by TNFα in PBMC of endometritic cows recorded in the study may indicate the development of endometritis in postpartum cows.

Circulating Mir-140 and leptin improve the accuracy of the differential diagnosis between psoriatic arthritis and rheumatoid arthritis: a case-control study

The differential diagnosis of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) is difficult because of the lack of diagnostic clinical signs and reliable biomarkers. This study investigated microRNAs (miRNA) and adipokines as potential additional markers to discriminate PsA from RA. The expression profile of miRNA (miR-21, miR-140, miR-146a, miR-155, miR-181b, miR-223, miR-let-7e) and inflammatory cytokines (IL-1β, IL-6, IL-17a, IL-23a, TNF-α) from peripheral blood mononuclear cells of PsA and RA patients compared to healthy controls (HC) were evaluated by real-time PCR, and serum adipokines (adiponectin, chemerin, leptin, resistin, visfatin) and cytokines by ELISA assay. Univariable binary logistic regression was used to find the association between PsA and potential predictors. The gene expression of miRNA and cytokines and the serum levels of adipokines were found significantly different in PsA and RA patients compared to HC, as well as in PsA versus RA. MiR-140 gene expression resulted up-regulated in PsA patients and reduced in RA in comparison to HC, and, for the first time, significantly higher in PsA compared with RA. Serum levels of IL-23a and leptin were significantly increased in PsA and RA populations than in HC, as well as in PsA versus RA. Furthermore, circulating TNF-α was up-regulated in PsA and RA in comparison to controls, while resulted higher in RA than in PsA. Univariable binary logistic regression analysis found the above-mentioned markers associated to PsA versus RA. Our results first demonstrated an increased expression of circulating miR-140 and serum leptin in PsA patients compared to RA, which were identified as potential additional biomarkers to discriminate PsA from RA. Since the differential diagnosis of PsA and RA poses challenges in clinical practice, our data may help to enhance the diagnostic performance of PsA in daily practice.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Two novel nomograms based on inflammatory cytokines or lymphocyte subsets to differentially diagnose severe or critical and Non-Severe COVID-19.

We intend to evaluate the differences of the clinical characteristics, cytokine profiles and immunological features in patients with different severity of COVID-19, and to develop novel nomograms based on inflammatory cytokines or lymphocyte subsets for the differential diagnostics for severe or critical and non-severe COVID-19 patients. We retrospectively studied 254 COVID-19 patients, 90 of whom were severe or critical patients and 164 were non-severe patients. Severe or critical patients had significantly higher levels of inflammatory cytokines than non-severe patients as well as lower levels of lymphocyte subsets. Significantly positive correlations between cytokine profiles were observed, while they were all significantly negatively correlated with lymphocyte subsets. Two effective nomograms were developed according to two multivariable logistic regression cox models based on inflammatory cytokine profiles and lymphocyte subsets separately. The areas under the receiver operating characteristics of two nomograms were 0.834 (95% CI: 0.779–0.888) and 0.841 (95% CI: 0.756–0.925). The bootstrapped-concordance indexes of two nomograms were 0.834 and 0.841 in training set, and 0.860 and 0.852 in validation set. Calibration curves and decision curve analyses demonstrated that the nomograms were well calibrated and had significantly more clinical net benefits. Our novel nomograms can accurately predict disease severity of COVID-19, which may facilitate the identification of severe or critical patients and assist physicians in making optimized treatment suggestions.