Interferon Gamma-induced Protein Research Articles

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients>3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Mitigation of CXCL10 secretion by metabolic disorder drugs in microglial-mediated neuroinflammation

Metabolic disorders are associated with several neurodegenerative diseases. We previously identified C-X-C motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10), as a major contributor to the type I interferon response in microglial-mediated neuroinflammation. Therefore, we hypothesized FDA-approved metabolic disorder drugs that attenuate CXCL10 secretion may be repurposed as a treatment for neurodegenerative diseases. Screening, dose curves, and cytotoxicity assays in LPS-stimulated microglia yielded treprostinil (hypertension), pitavastatin (hyperlipidemia), and eplerenone (hypertension) as candidates that significantly reduced CXCL10 secretion (in addition to other pro-inflammatory mediators) without impacting cell viability. Altogether, these data suggest metabolic disorder drugs that attenuate CXCL10 as potential treatments for neurodegenerative disease through mitigating microglial-mediated neuroinflammation.

The role of IFI16 in regulating PANoptosis and implication in heart diseases.

Interferon Gamma Inducible Protein 16 (IFI16) belongs to the HIN-200 protein family and is pivotal in immunological responses. Serving as a DNA sensor, IFI16 identifies viral and aberrant DNA, triggering immune and inflammatory responses. It is implicated in diverse cellular death mechanisms, such as pyroptosis, apoptosis, and necroptosis. Notably, these processes are integral to the emergent concept of PANoptosis, which encompasses cellular demise and inflammatory pathways. Current research implies a significant regulatory role for IFI16 in PANoptosis, particularly regarding cardiac pathologies. This review delves into the complex interplay between IFI16 and PANoptosis in heart diseases, including atherosclerosis, myocardial infarction, heart failure, and diabetic cardiomyopathy. It synthesizes evidence of IFI16's impact on PANoptosis, with the intention of providing novel insights for therapeutic strategies targeting heart diseases.

Quantitative and qualitative analysis of stability for 16 serum immunoregulators over 50 freeze-thaw cycles.

To evaluate the reliability of data from the assay of bio-archived specimens, a 50-freeze-thaw-cycle (FTC) degradation study of fresh sera was conducted to test the stability of 16 immunoregulators. Twenty de-identified serum specimens were obtained from volunteers at United Health Services-Wilson Memorial Hospital. Specimens were stored at -20°C and underwent daily 1 h thawing and subsequent freezing for each FTC over 50 consecutive days. Immunoregulator concentrations were assessed via enzyme-linked immunosorbent assay (ELISA) in participant samples at 2 FTC (baseline), 25 FTC, and 50 FTC. Specific immunoregulators observed in the study were C-reactive protein (CRP), interleukin (IL)-1α, 4, 6, 8, 10, monocyte chemoattractant protein-1 (MCP-1, CCL2), monocyte chemoattractant protein-2 (MCP-2, CCL8), eotaxin-1, thymus-and-activation-regulated chemokine (TARC, CCL17), regulated on activation normal T-cell expressed and secreted (RANTES, CCL5), growth-regulated oncogene-alpha (GRO-α, CXCL1), small inducible cytokine A1 (I-309, CCL1), interferon-gamma (IFN-γ), interferon-gamma inducible protein-10 (IP-10, CXCL10), and tumor necrosis factor-alpha (TNF-α). Quantitative stability of serum immunoregulators: Serum CRP, IL-8, IL-10, IFN-γ, IP-10, and eotaxin-1 levels appear to be statistically equivalent from baseline to 50 FTC (p ≤ .05). Retention of patterns in serum immunoregulators: patterns across FTC were retained for TARC (age) and CRP, IFN-γ, and MCP-2 (sex). While the effect of multiple FTC on serum immunoregulator levels may not replicate prolonged freezer storage, the results of this study provide valuable information on the robustness of immunoregulators for research using bio-archived sera.

Interferon-gamma contributes to disease progression in the Ndufs4(-/-) model of Leigh syndrome.

Leigh syndrome (LS), the most common paediatric presentation of genetic mitochondrial dysfunction, is a multi-system disorder characterised by severe neurologic and metabolic abnormalities. Symmetric, bilateral, progressive necrotizing lesions in the brainstem are defining features of the disease. Patients are often symptom free in early life but typically develop symptoms by about 2 years of age. The mechanisms underlying disease onset and progression in LS remain obscure. Recent studies have shown that the immune system causally drives disease in the Ndufs4(-/-) mouse model of LS: treatment of Ndufs4(-/-) mice with the macrophage-depleting Csf1r inhibitor pexidartinib prevents disease. While the precise mechanisms leading to immune activation and immune factors involved in disease progression have not yet been determined, interferon-gamma (IFNγ) and interferon gamma-induced protein 10 (IP10) were found to be significantly elevated in Ndufs4(-/-) brainstem, implicating these factors in disease. Here, we aimed to explore the role of IFNγ and IP10 in LS. To establish the role of IFNγ and IP10 in LS, we generated IFNγ and IP10 deficient Ndufs4(-/-)/Ifng(-/-) and Ndufs4(-/-)/IP10(-/-) double knockout animals, as well as IFNγ and IP10 heterozygous, Ndufs4(-/-)/Ifng(+/-) and Ndufs4(-/-)/IP10(+/-), animals. We monitored disease onset and progression to define the impact of heterozygous or homozygous loss of IFNγ and IP10 in LS. Loss of IP10 does not significantly impact the onset or progression of disease in the Ndufs4(-/-) model. IFNγ loss significantly extends survival and delays disease progression in a gene dosage-dependent manner, though the benefits are modest compared to Csf1r inhibition. IFNγ contributes to disease onset and progression in LS. Our findings suggest that IFNγ targeting therapies may provide some benefits in genetic mitochondrial disease, but targeting IFNγ alone would likely yield only modest benefits in LS.

Associations of the circulating levels of cytokines with the risk of myeloproliferative neoplasms: a bidirectional mendelian-randomization study

ObjectiveIn the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms.MethodsA genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl).ResultsOur results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03–1.81, P = 0.032; OR = 1.55,95%CI = 1.09–2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002–0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018).ConclusionOur findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.

The Influence of Neodymium-Doped Yttrium Aluminum Garnet Laser Pulse Repetition Rate on Cytokine Secretion from Peripheral Blood Mononuclear Cells in Vitro

Objective: Biological effects of infrared laser energy at various exposure parameters have been characterized in previous in vitro and animal studies. However, the impact of pulse repetition rate (PRR) has not been evaluated in this context. The purpose of this investigation was to assess the influence of PRR on cytokine secretion from peripheral blood mononuclear cells (PBMCs) subjected to pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser energy. Materials and Methods: Rat PBMCs were cultured in vitro then stimulated using a lipopolysaccharide concentration of 0 or 100 ng/ml. Cultures received Nd:YAG laser radiation (1064 nm, 5 W, 30 s) at PRR of 0 (untreated controls), 20, 30, 40, or 60 Hz. Concentrations of tumor necrosis factor-α (TNF-α), macrophage inflammatory protein (MIP)-1α, macrophage inflammatory protein (MIP)-2, monocyte chemoattractant protein-1 (MCP-1), interferon-gamma-induced protein (IP)-10, interleukin (IL)-6, and IL-10 were recorded using a magnetic microsphere immunoassay. The main effects of PRR and LPS stimulation on cytokine concentrations, and the interaction between PRR and LPS stimulation, were assessed using two-way analysis of variance. Bonferroni post hoc tests were used to identify pairwise differences between groups. Results: The main effect of PRR was statistically significant for MIP-1α (P = 0.018), TNF-α (P = 0.025), MCP-1 (P < 0.001), MIP-2 (P = 0.013), and IL-6 (P = 0.031). Five of six pro-inflammatory cytokines exhibited significantly lower mean concentrations in laser-exposed compared with control cultures at one or more PRR. However, no statistically significant differences were found between PRR groups. Conclusions: Under the described conditions, statistically significant differences in cytokine secretion were observed between laser-exposed and control cultures, consistent with prior reports. However, PRR appears to be an irrelevant factor in immunomodulation of PBMCs.

Voluntary exercise preserves visual function and reduces inflammatory response in an adult mouse model of autosomal dominant retinitis pigmentosa

Whole-body physical exercise has been shown to promote retinal structure and function preservation in animal models of retinal degeneration. It is currently unknown how exercise modulates retinal inflammatory responses. In this study, we investigated cytokine alterations associated with retinal neuroprotection induced by voluntary running wheel exercise in a retinal degeneration mouse model of class B1 autosomal dominant retinitis pigmentosa, I307N Rho. I307N Rho mice undergo rod photoreceptor degeneration when exposed to bright light (induced). Our data show, active induced mice exhibited significant preservation of retinal and visual function compared to inactive induced mice after 4 weeks of exercise. Retinal cytokine expression revealed significant reductions of proinflammatory chemokines, keratinocyte-derived chemokine (KC) and interferon gamma inducible protein-10 (IP-10) expression in active groups compared to inactive groups. Through immunofluorescence, we found KC and IP-10 labeling localized to retinal vasculature marker, collagen IV. These data show that whole-body exercise lowers specific retinal cytokine expression associated with retinal vasculature. Future studies should determine whether suppression of inflammatory responses is requisite for exercise-induced retinal protection.

Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

Genetic liability to elevated circulating IP-10, IFNγ and SCGFβ levels in relation to thoracic aortic aneurysm: A mendelian randomization study

Inflammation is associated with thoracic aortic aneurysm (TAA) but the effects of each circulating inflammatory factor on TAA remain unclear. In this study, we explored the relationship between circulating inflammatory factors and TAA risk using Mendelian randomization (MR) approach based on summary statistics from the latest genome-wide association study (GWAS) of 41 circulating inflammatory factors in 8293 Finns and a GWAS involving 1351 TAA cases and 18,295 controls of European ancestry. In univariable MR, higher interferon gamma-induced protein 10 (IP-10) levels, higher interferon gamma (IFNγ) levels and higher stem cell growth factor beta (SCGFβ) levels were associated with an increased risk of TAA (OR = 1.37, 95 % CI = 1.17–1.59, p = 7.42 × 10−5; OR = 1.43, 95 % CI = 1.19–1.74, p = 2.04 × 10−4; OR = 1.27, 95 % CI = 1.09–1.48, p = 2.40 × 10−3, respectively). In multivariable MR, the patterns of associations for the three cytokines remained adjusting for each other or smoking, but were attenuated differently with adjustment for other cardiovascular risk factors, especially for lipids and body mass index. Bidirectional MR approach did not identify any significant associations between cytokines and risk factors. Our results indicated that circulating cytokines may play mediation roles in the pathogenesis of TAA. Further studies are needed to determine whether these biomarkers can be used to prevent and treat TAA.

Comprehensive analysis of the role of interferon gamma-inducible protein 30 on immune infiltration and prognosis in clear cell renal cell carcinoma.

Although the immune factor interferon gamma-inducible protein 30 (IFI30) has been linked to the growth and immune infiltration of various malignancies, its function and mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. We used several databases to detect and validate IFI30 expression in ccRCC and its connection to immune invasion. We found that IFI30 expression was higher in ccRCC tissues compared to normal tissues, and was strongly associated with tumor grade, T stage, and M stage. Univariate and multivariate analyses showed that ccRCC cases with lower IFI30 expression levels had a higher OS rate than those with high IFI30 expression (P < 0.05). Additionally, we collected a total of 104 cases of ccRCC and adjacent tissues from the First Affiliated Hospital of Jinzhou Medical University between January 2018 and January 2020 for immunohistochemical (IHC) analysis, along with their relevant clinicopathological data. The relationship between IFI30 and expression of CD3E, CD4, CD8A, interleukin 10 (IL-10) and transforming growth factor beta (TGFB2) was examined using the ccRCC data from The Cancer Genome Atlas (TCGA) database, with findings verified by IHC analysis using the collected cases. Statistical analysis performed with SPSS found the positive correlation between the expression of CD3E, CD4, CD8A and IL-10 and the IFI30 expression, and negative correlation of TGFB2 expression with the IFI30 expression in ccRCC. Concurrently, a notable association was observed between high IFI30 expression and immune cell infiltration in ccRCC. High IFI30 expression is connected to the ccRCC's poor prognosis with the infiltration of immune cell. These findings suggest that high IFI30 expression could serve as a marker of poor prognosis and be associated with immune cell infiltration in ccRCC.

Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis.

Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia-related traits using genetic data. A two-sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome-wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR-PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR-Egger regression, and "leave-one-out" sensitivity analyses. The IVM-MR analysis showed a casual association between genetically predicted circulating levels of interleukin-16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980-1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948-0.995, p = .020). Additionally, interferon-gamma-induced protein 10 (IP-10), interleukin-1-beta (IL-1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin-12 (IL-12), and interleukin-5 (IL-5) with grip strength. Comparable results were confirmed via the MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates. The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.

Characterizing of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta marked by elevated amniotic fluid interferon gamma-induced protein 10 (IP-10) in pregnancies complicated by preterm prelabor rupture of membranes

ObjectivesThis study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of interferon gamma-induced protein 10 (IP-10) (≥2200 pg/mL) in the amniotic fluid of women with preterm prelabor rupture of membranes (PPROM). Specifically, the study investigated whether these intra-amniotic inflammatory changes were more common in women with microbial invasion of amniotic cavity (MIAC) and intra-amniotic inflammation (IAI), as indicated by increased amniotic fluid interleukin (IL)-6 concentration (≥3000 pg/mL). Study designA cohort of 114 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation were included. Amniotic fluid samples were obtained via amniocentesis upon admission. MIAC diagnosis involved aerobic and anaerobic cultures, as well as polymerase chain reaction (PCR) analysis of the amniotic fluid. Immunoassay tests and enzyme-linked immunosorbent assay (ELISA) were used to determine IL-6 and IP-10 concentrations, respectively. ResultsAmong the participants, 19.3 % and 15.8 % had MIAC and IAI, respectively. The occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was similar between women with and without MIAC (25 % vs. 40.9 %, p = 0.136, adjusted p = 0.213). The rate of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was significantly higher in women with IAI compared to those without, after adjusting for gestational age at sampling (55.6 % vs. 22.9 %, p = 0.005, adjusted p = 0.011). ConclusionThis study revealed comparable rates of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with and without MIAC, but a higher prevalence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with IAI. These findings suggest involvement of chronic inflammation even in women with PPROM with acute intra-amniotic inflammation.

Combined analysis of host IFN-γ, IL-2 and IP-10 as potential LTBI biomarkers in ESAT-6/CFP-10 stimulated blood

Background: Accurate diagnosis of latent tuberculosis infected (LTBI) individuals is important in identifying individuals at risk of developing active tuberculosis. Current diagnosis of LTBI routinely relies on the detection and measurement of immune responses using the Tuberculin Skin Test (TST) and interferon gamma release assays (IGRAs). However, IGRA, which detects Mycobacterium tuberculosis specific IFN-γ, is associated with frequent indeterminate results, particularly in immunosuppressed patients. There is a need to identify more sensitive LTBI point of care diagnostic biomarkers. The aim of this study was to assess the validity of early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) stimulated plasma to identify additional cytokines and chemokines as potential biomarkers of LTBI.Method: The levels of 27 cytokines and chemokines were measured by Bio-Plex Pro cytokine, chemokine and growth factor assay in ESAT-6 and CFP-10 co-stimulated plasma from 20 LTBI participants with positive IGRA (Quantiferon TB Gold plus) and 20 healthy controls with negative IGRA. Traditional ELISA was used to validate the abundance of the best performing markers in 70 LTBI and 72 healthy participants. All participants were HIV negative.Results: We found that Interleukin 1 receptor antagonist (IL1ra) (p = 0.0056), Interleukin 2 (IL-2) (p &amp;lt; 0.0001), Interleukin 13 (IL-13) (p &amp;lt; 0.0001), Interferon gamma-induced protein 10 (IP-10) (p &amp;lt; 0.0001), and Macrophage inflammatory protein-1 beta (MIP1b) (p = 0.0010) were significantly higher in stimulated plasma of LTBI compared to healthy individuals. Stimulated plasma IL-2 (cutoff 100 pg/mL), IP-10 (cutoff 300 pg/mL) and IL-13 (5 pg/mL) showed potential in diagnosing LTBI with PPV = 100%, 0.89.4%, and 80.9% and NPV = 86.9%, 0.85.7%, and 84.2%, respectively.Conclusion: Our data shows that co-stimulating whole blood with ESAT-6 and CFP-10 may help distinguish LTBI from healthy individuals. We also identified IL-2 and IP-10 as potential biomarkers that could be added to the currently used IFN-γ release assays in detection of LTBI.

IP-10 for the Diagnosis and Treatment Monitoring of Tuberculosis in Children.

To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring.

Association of denosumab with serum cytokines, chemokines, and bone-related factors in patients with rheumatoid arthritis: A post hoc analysis of a multicentre, open-label, randomised, parallel-group study.

To clarify changes in serum cytokines, chemokines, and bone-related factors during denosumab treatment in rheumatoid arthritis (RA) patients. This was a post hoc analysis of a multicentre, open-label, randomised, parallel-group study. Patients were randomly assigned to continue treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) plus receive treatment with denosumab (csDMARDs plus denosumab group) or to continue treatment with csDMARD therapy alone for 12 months. Serum biomarker levels were measured at baseline and 6 and 12 months. Baseline and 6-month data from the csDMARDs plus denosumab (n = 22) and csDMARD therapy alone (n = 22) groups were analysed. Statistically significant changes from baseline were seen: dickkopf-related protein 1 decreased at 6 and 12 months (both groups); osteopontin decreased at 6 months in the csDMARDs plus denosumab group; osteopontin and soluble CD40 ligand increased at 6 and 12 months in the csDMARD therapy alone group; osteocalcin decreased at 6 and 12 months, epidermal growth factor decreased at 12 months, and macrophage-derived chemokine decreased at 6 months in the csDMARDs plus denosumab group; and interferon gamma-induced protein-10 increased at 12 months in the csDMARD therapy alone group. Denosumab may inhibit bone destruction by suppressing bone-related factors/chemokines.

Toxoplasma gondii infection and brain inflammation: A two-sample mendelian randomization analysis

BackgroundToxoplasma gondii is an opportunistic parasitic protozoan that can cause highly fatal toxoplasmic encephalitis when the host immune system is compromised. However, the transition from chronic to acute infection remains poorly understood. In this study, we conducted a 180-day observation of tissue damage and inflammation in the brains of mice infected with T. gondii. Subsequently, we investigated the inflammatory factors that T. gondii infection may alter using two-sample Mendelian randomization (MR) analysis. MethodsWe first established a mouse model of T. gondii infection. Subsequently, the mice were euthanized, the brain tissue collected, and immunohistochemistry and hematoxylin and eosin staining performed to observe tissue damage and inflammatory conditions at various time points. Our study also included a published large-scale genome-wide association study meta-analysis that encompassed the circulating concentrations of 41 cytokines. This dataset included 8293 individuals from three independent population cohorts in Finland. Genetic association data for T. gondii were sourced from the Integrative Epidemiology Unit and European Bioinformatics Institute datasets, which included 5010 and 559 individuals of European ancestry, respectively. To assess the causal relationship between T. gondii infection and inflammatory biomarkers, we applied a two-sample MR. ResultsInflammation and damage resulting from T. gondii infection varied among the distinct regions of the mouse brain. Based on the MR analysis results, three inflammatory biomarkers were chemically assigned to Chemokines and Others, including IP10 (interferon gamma inducible protein-10), MCP1 (monocyte chemoattractant protein-1), and TRAIL (TNF-related apoptosis-inducing ligand). ConclusionOur study commenced with the assessment of tissue damage and progression of inflammation in distinct regions of the mouse brain after T. gondii infection. Subsequently, using MR analysis, we detected potential alterations in inflammatory factors associated with this infection. These findings offer valuable insights into the mechanisms underlying toxoplasmic encephalitis and suggest directions for the prevention and treatment of T. gondii infections.

Saliva-Based Protein Analysis in Pediatric Dentofacial Inflammation.

Saliva contains various proteins that are important in developing inflammatory processes and their prevention. One key aspect of saliva research is the relationship between oral infections and inflammation, and the role of some salivary proteins. To demonstrate which salivary cytokines can be biomarkers of acute odontogenic oral and facial infections in children. The study included two groups of patients: a study group of 28 children: 7 girls and 21 boys aged 3 -17 years with acute dentofacial inflammation (DI) and a control group of 52 children: 16 girls and 36 boys aged 4-17 years with uncomplicated dental caries (CE). The levels of Interleukin-5 (IL-5), Interleukin -10 (IL-10), Interleukin-17A (IL-17A), Interleukin-12p70 (IL-12p70), Eotaxin, Rantes, Vascular Endothelial Growth Factor (VEGF), and Interferon gamma-induced protein 10 (IP10) in the saliva of children in DI and CE groups were compared. Statistical analysis was performed with Statistica 13. The Student's t-test and the Wilcoxon signed-rank test were used. The results show that IL-10, IL-17A, and Eotaxin showed a statistically significant increase in the DI group compared to the CE group. The significance level for IL-10 was p=0.02, for IL-17A was equal to Eotaxin and p=0.04. The other measured parameters did not differ statistically significant between the two groups. IL-10, IL-17A, and Eotaxin can be used as potential biomarkers for tooth-related inflammatory states of the oral cavity and face in children. These biomarkers can be useful in identifying and monitoring the presence of inflammation in the oral cavity and face.

Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis

Background. Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis. Methods. In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients. Results. IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1β concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (P = 0.003) concentrations from POD 1 and elevated IL-8 (P = 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (P &lt; 0.001) and IL-8 (P = 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected. Conclusions. Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.