Macrophage Inflammatory Protein-1alpha Research Articles

Comparison of serum cytokines and chemokines levels and clinical significance in patients with pemphigus vulgaris-A retrospective study.

In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti-desmoglein (Dsg) 1 antibody, anti-Dsg3 antibody and co-infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high-throughput cytokine detection method). Additionally, anti-Dsg1 and anti-Dsg3 antibodies were determined through enzyme-linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)-1RA, IL-1β, IL-2, IL-12p70, GM-CSF, TNF-α, IL-18, IFN-γ), Th2 cytokines (IL-5, IL-10, IL-13) and Th17/Th22-related cytokines (IL-17A, IL-22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), stromal cell-derived factor-1 alpha (SDF-1α), interferon-inducible protein-10 (IP-10), Regulated on Activation in Normal T-Cell Expressed And Secreted (RANTES), growth-regulated on-gene-alpha (GRO-α), MIP-1β) and Th2 (IL-31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL-7, IFN-γ, IL-18 and GRO-α showed positive correlations with PDAI, IL-6 correlated positively with anti-Dsg3 antibody levels, and IL-12p70, IL-18, and IFN-γ correlated positively with anti-Dsg1 antibody levels. Furthermore, IL-15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1-related cytokines.

Biomarkers in periodontal health and diseases

Cause of tooth loss in world is periodontitis which is a bacterial infection whose pathogenesis has complex immune response. The diagnosis is based upon patient’s periodontal health, full mouth bleeding score, full mouth plaque score, probing depth, clinical attachment level, bleeding on probing, recessions, mobility, and migration. For early diagnosis of periodontitis chair side diagnostic tests are available which are used by periodontist. There are many biomarkers for periodontitis which help in early detection like: MMP-8 (Metalloproteinase-8), MIP-1α (Macrophage inflammatory protein-1 alpha), IL-1 β (Interleukin-1beta), IL-6 (Interleukin-6), and HB (Hemoglobin), and their combinations.

IP-10, MIP1α, IL-6, and IL-1β as Biomarkers Associated with Disease Severity of COVID-19

Background: The factors responsible for the progression of COVID-19 from a mild illness to a severe and often lethal condition, characterized by respiratory failure and multiple organ involvement, remain unclear. The identification of biomarkers capable of predicting disease progression is of the highest importance. Objectives: This study sought to assess laboratory measurements of interferon-gamma inducible protein-10 (IP-10), macrophage inflammatory protein 1-alpha (MIP1α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) to achieve this objective. Methods: We measured IP-10 and MIP1α by qRT-PCR and IL-6 and IL-1β using an enzyme-linked immunosorbent assay in 120 serum samples. We analyzed differences between patients with moderate, severe, and recovered COVID-19. Results: The number of positive cases for biomarkers IP-10, MIP1α, IL-6, and IL-1β were significantly different between groups. The expression levels of IP-10 and MIP1α were significantly higher in patients with severe COVID-19 compared to those who had recovered. A strong positive association was observed between IP-10 and MIP1α in severe infection cases. Additionally, these biomarkers were relatively independent predictors of disease severity. Conclusions: The results suggest that IP-10, MIP1α, IL-6, and IL-1β are promising research candidates for understanding the severity of COVID-19 and for investigating possible pathophysiological mechanisms of the disease.

Causal association between circulating inflammatory cytokines and intracranial aneurysm and subarachnoid hemorrhage.

The causal association between inflammatory cytokines and the development of intracranial aneurysm (IA), unruptured IA (uIA) and subarachnoid hemorrhage (SAH) lacks clarity. The summary-level datasets for inflammatory cytokines were extracted from a genome-wide association study of the Finnish Cardiovascular Risk in Young Adults Study and the FINRISK survey. The summary statistics datasets related to IA, uIA and SAH were obtained from the genome-wide association study meta-analysis of the International Stroke Genetics Consortium and FinnGen Consortium. The primary method employed for analysis was inverse variance weighting (false discovery rate), supplemented by sensitivity analyses to address pleiotropy and enhance robustness. In the International Stroke Genetics Consortium, 10, six and eight inflammatory cytokines exhibited a causal association with IA, uIA and SAH, respectively (false discovery rate, p < 0.05). In FinnGen datasets, macrophage Inflammatory Protein-1 Alpha (MIP_1A), MIP_1A and interferon γ-induced protein 10 (IP_10) were verified for IA, uIA and SAH, respectively. In the reverse Mendelian randomization analysis, the common cytokines altered by uIA and SAH were vascular endothelial growth factor (VEGF), MIP_1A, IL_9, IL_10 and IL_17, respectively. The meta-analysis results show that MIP_1A and IP_10 could be associated with the decreased risk of IA, and MIP_1A and IP_10 were associated with the decreased risk of uIA and SAH, respectively. Notably, the levels of VEGF, MIP_1A, IL_9, IL_10 and TNF_A were increased with uIA. Comprehensive heterogeneity and pleiotropy analyses confirmed the robustness of these results. Our study unveils a bidirectional association between inflammatory cytokines and IA, uIA and SAH. Further investigations are essential to validate their relationship and elucidate the underlying mechanisms.

Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization.

Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] and tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess the causal relationship between 41 inflammatory cytokines and KOA using Mendelian randomization (MR). Two-sample bidirectional MR was performed using genetic variation data for 41 inflammatory cytokines that were obtained from European Genome-Wide Association Study (GWAS) data (n=8293). KOA-related genetic association data were also obtained from European GWAS data (n=40,3124). Inverse variance weighting (IVW), MR, heterogeneity, sensitivity, and multiple validation analyses were performed. Granulocyte colony-stimulating factor (G-CSF) or colony-stimulating factor 3 (CSF-3) levels were negatively associated with the risk of developing KOA (OR: 0.93, 95%CI:0.89-0.99, P=0.015). Additionally, macrophage inflammatory protein-1 alpha (MIP-1A/CCL3) was a consequence of KOA (OR: 0.72, 95%CI:0.54-0.97, P=0.032). No causal relationship was evident between other inflammatory cytokines and KOA development. This study suggests that certain inflammatory cytokines may be associated with KOA etiology. G-CSF exerts an upstream influence on KOA development, whereas MIP-1A (CCL-3) acts as a downstream factor.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Retrospective Case Study on the Evaluation of Inflammatory Markers, Macrophage Inhibitory Protein-1α and Interferon-γ in Sleep Deprivation Condition

ABSTRACT Background and Aim: Sleep is an important physiological process that is necessary for the normal functioning of the body. Sleep greatly affects all aspects of our body, including the immune pathways or immune response system of our body, which plays a determinant role in the development and progression of chronic inflammatory diseases. In this study, we worked to find the relation between sleep deprivation and levels of pro-inflammatory markers macrophage inflammatory protein 1-alpha (MIP-1α) and interferon gamma (IFN-γ). To find the relation between sleep deprivation and levels of pro-inflammatory markers MIP-1α and IFN-γ. Objective: To find the relation between sleep deprivation and levels of pro-inflammatory markers MIP-1α and IFN-γ. Materials and Methods: The study was conducted with 40 individuals as participants, of which 20 were sleep-deprived (SD), and 20 had adequate amounts of sleep. The sleep duration details of the individuals were obtained by questionnaire. Blood was withdrawn from all the subjects after due consent from them. Plasma was separated and was used to evaluate their MIP-1α levels and IFN-γ levels. Results: The MIP-1α levels and levels of IFN-γ were found to be significantly elevated in the SD individuals than that of individuals who had adequate sleep. Conclusion: Sleep loss and sleep deprivation are associated with altered expressions of key regulatory factors and upregulation of pro-inflammatory cytokines production. Thus, sleep deprivation can be considered to be one of the major contributors to the development and progression of various chronic inflammatory diseases.

Abatacept decreases renal T-cell infiltration and renal inflammation and ameliorates progressive renal injury in obese Dahl salt-sensitive rats before puberty.

Prepubertal obesity (PPO) is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats was associated with increased T-cell infiltration and activation prior to puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SSLepRmutant rats before puberty. Four-week-old SS and SSLepRmutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T-cells by almost 50% in SSLepRmutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha (MIP-3α) while increasing IL-4 in SSLepRmutant rats without affecting SS rats. While not having an impact on blood glucose, abatacept reduced hyperinsulinemia and plasma triglycerides in SSLepRmutant rats without affecting SS rats. We did not observe any differences in MAP among the groups. Proteinuria was markedly higher in SSLepRmutant rats versus SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SSLepRmutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SSLepRmutant rats vs SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SSLepRmutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with PPO.

Prognostic Value of Macrophage Inflammatory Protein-3alpha (MIP3-Alpha) and Severity Scores in Elderly Patients with Sepsis.

This study examines the effectiveness of MIP-3alpha and severity scores in determining the prognosis of elderly sepsis patients. From October 2020 to April 2021, a total of 171 elderly sepsis patients were admitted to the Emergency Department of the Shijingshan Branch of Beijing Chaoyang Hospital, Capital Medical University. According to the 28-day mortality rate, they were divided into two groups: survivors (48 cases) and deaths (123 cases). At admission, severity scores which are the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were calculated. Thelogistic regression was used to analyze the independent risk factors associated with 28-day mortality in elderly sepsis patients. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the value of MIP-3alpha, SOFA, and APACHE II in the evaluation of 28-day mortality in elderly sepsis patients. MIP-3alpha, SOFA and APACHE II of the death group were significantly higher than those of the survival group (P < 0.05). Multivariate logistic regression analysis showed that MIP-3alpha, SOFA, APACHE II, and systolic blood pressure (SBP) were independent risk factors for 28-day mortality of senile sepsis (P < 0.05). Analysis of the ROC curve revealed that MIP-3alpha, SOFA, APACHE II had predictive value for the 28-day prognosis of senile sepsis (all P < 0.01). Combing with MIP-3alpha and SOFA showed better predictive ability (Z1 = 3.733, Z2 = 2.996, both P < 0.01), compared to detecting MIP-3alpha and SOFA alone. In senile sepsis, MIP-3alpha, SOFA, APACHE II and SBP are independent risk factors for 28-day mortality. The combination of MIP-3alpha and SOFA can further enhance the predictive value of 28-day mortality in patients with senile sepsis and provide some reference value for the evaluation and treatment of senile sepsis.

Salivary levels of inflammatory and anti-inflammatory biomarkers in periodontitis patients with and without acute myocardial infarction: implications for cardiovascular risk assessment.

Periodontitis is initiated by a dysbiotic activity and furthermore leads to a chronic inflammatory response. The presence of pro-inflammatory markers plays an important role in the inflammatory load. Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro- inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 h of AMI. Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Our study provides possible evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

The effect of the interaction of sleep onset latency and age on ischemic stroke severity via inflammatory chemokines.

Prolonged sleep onset latency (PSOL) and age have been linked to ischemic stroke (IS) severity and the production of chemokines and inflammation, both of which contribute to IS development. This study aimed to explore the relationship between chemokines, inflammation, and the interplay between sleep onset latency (SOL) and age in influencing stroke severity. A cohort of 281 participants with mild to moderate IS was enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and SOL was recorded. Serum levels of macrophage inflammatory protein-1alpha (MIP-1α), macrophage inflammatory protein-1beta (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured. NIHSS scores of middle-aged participants with PSOL were significantly higher than those with normal sleep onset latency (NSOL) (p = 0.046). This difference was also observed when compared to both the elderly with NSOL (p = 0.022), and PSOL (p < 0.001). Among middle-aged adults with PSOL, MIP-1β exhibited a protective effect on NIHSS scores (β = -0.01, t = -2.11, p = 0.039, R2 = 0.13). MIP-1α demonstrated a protective effect on NIHSS scores in the elderly with NSOL (β = -0.03, t = -2.27, p = 0.027, R2 = 0.12). This study reveals a hitherto undocumented association between PSOL and IS severity, along with the potential protective effects of MIP-1β in mitigating stroke severity, especially among middle-aged patients.

Feeding spray-dried plasma to broilers early in life improved their intestinal development, immunity and performance irrespective of mycotoxins in feed.

Fungi that produce mycotoxins can grow on certain food products, such as grains and feed, and can cause a variety of health issues if consumed by animals, including chickens. The use of spray-dried plasma (SDP) is one strategy for combating the health problems caused by mycotoxins. In the present study, Ross 308 chickens (n = 960) were divided into four treatment groups. T1 group was given a control diet (corn-soybean meal), T2 group was given a control diet +2% SDP, T3 group was given a control diet +2% SDP + mixture mycotoxins and T4 group was givena control diet + mycotoxin mixture. The presence of SDP resulted in weight gain and decreased feed efficiency, whereas mycotoxins resulted in weight loss and increased feed efficiency. SDP increased the thymus' relative weight. The presence of mycotoxins increased the heterophile/lymphocyte ratio. The presence of mycotoxins reduced the production of IL-2 and macrophage inflammatory protein-3 Alpha (MIP-3a), whereas the presence of SDP increased the production of macrophage colony-stimulating Factor (M-CSF). SDP resulted in higher IgA concentrations in the intestinal and tracheal washes than mycotoxin. Finally, adding SDP to broiler diets boosts weight gain, feed efficiency, and immune system development. Our results provide information supporting that SDP is a promising tool for improving poultry immunity and performance.

Cognitive inflexibility and immunome biomarkers in children with autism spectrum disorder

Cognitive inflexibility is a transdiagnostic endophenotype that presents across a range of disorders, including autism spectrum disorder (ASD), which is maintained through adulthood, and encompasses both cognitive and behavioral rigidity. There is evidence for immune dysfunction in a subgroup of ASD, including systemic inflammation, cytokine dysregulation and anti-brain autoantibodies. Although immunome pathways are involved in ASD pathophysiology, there is little known about how they relate to symptom domains or symptom severity, and whether such biomarkers may be useful in optimizing future clinical trials. We correlated baseline clinical measures of cognitive inflexibility and resultant irritability with immunome biomarker levels in children with ASD, aged 5–18 years with ABC-I scores ≥18, CGI-S scores ≥4 and SRS-2 scores ≥66T, at Albert Einstein College of Medicine (AECOM). Non-parametric Spearman correlations and estimated multivariable regression analyses adjusting for potential confounders, including other clinical variables, race, sex, and age were completed. Strong positive correlations (rs > .70) were found between the Montefiore Einstein Rigidity Scale – Revised (MERS-R) Total Score and the pro-inflammatory cytokines IL-6 (rs=.80), granulocyte-colony stimulating factor (GCSF; rs =.72), macrophage inflammatory protein-1 alpha (MIP-1a; rs =.71). The MERS-R subscales also had moderate and strong correlations with the immunome biomarkers. The MERS-R Total Rigidity Subscale Score had a strong positive relationship with IL-6 (rs = 0.7856). Using multivariable regression analyses significant relationships were found between the MERS-R Total Rigidity Subscale Score and proinflammatory cytokine IL-18 (p = 0.02), and a nonsignificant trend was found between it and IFN-alpha2 (β = −4.982, p = 0.058). The ABC-I was significantly correlated with pro-inflammatory cytokine IL-18 (p = .013), IFN-alpha2 (p = 0.039), the anti-inflammatory cytokine IL-10 (p = 0.02), and adaptive immunity cytokine IL-2 (p = 0.041). This preliminary data is the first to examine the relationship of clinical measures of cognitive inflexibility and immunome biomarkers in children with ASD, and may provide a framework for better understanding the relationship between immunome mechanisms, cognitive inflexibility, and ASD symptomatology. Clinicaltrials.gov: NCT03202303.

Biological effects of molybdenum(IV) sulfide nanoparticles and microparticles in the rat after repeated intratracheal administration.

In this study, molybdenum(IV) sulfide (MoS2 ) nanoparticles (97 ± 32 nm) and microparticles (1.92 ± 0.64 μm) stabilized with poly (vinylpolypyrrolidone) (PVP) were administered intratracheally to male and female rats (dose of 1.5 or 5mg/kg bw), every 14 days for 90 days (seven administrations in total). Blood parameters were assessed during and at the end of the study (hematology, biochemistry including glucose, albumins, uric acid, urea, high density lipoprotein HDL, total cholesterol, triglycerides, aspartate transaminase, and alanine transaminase ALT). Bronchoalveolar lavage fluid (BALF) analyses included cell viability, biochemistry (total protein concentration, lactate dehydrogenase, and glutathione peroxidase activity), and cytokine levels (tumor necrosis factor α, TNF-α, macrophage inflammatory protein 2-alpha, MIP-2, and cytokine-induced neutrophil chemoattractant-2, CINC-2). Tissues were subjected to routine histopathological and electron microscopy (STEM) examinations. No overt signs of chronic toxicity were observed. Differential cell counts in BALF revealed no significant differences between the animal groups. An increase in MIP-2 and a decrease in TNF-α were observed in BALF in the exposed males. The histopathological changes in the lung evaluated according to a developed classification system (based on severity of inflammation, range 0-4, with 4 indicating the most severe changes) showed average histopathological score of 1.33 for animals exposed to nanoparticles and microparticles at the lower dose, 1.72 after exposure to nanoparticles at the higher dose, and 2.83 for animals exposed to microparticles at the higher dose. In summary, it was shown that nanosized and microsized MoS2 can trigger dose-dependent inflammatory reactions in the lungs of rats after multiple intratracheal instillation irrespective of the animal sex. Some evidence indicates a higher lung pro-inflammatory potential of the microform.

Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study

To investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men. Eighteen individuals were classified as normal weight (NW; n=9 - age: 25±5 and BMI: 21.4±1.7) and overweight/obese (OW; n=9 - age: 29±7 and BMI: 29.2±2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-β1 and β2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR). Individuals with overweight/obese (OW) presented higher glucose (P=0.009) and leptin (P=0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P=0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P=0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-β2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P=0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3+CD4+ T cells (P=0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8+ T cells (P=0.001) than NW. Central obesity promoted reductions in interleukin 10 production response and increase in AR-β2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults.

The PPARα agonist fenofibrate reduces the cytokine imbalance in a maternal immune activation model of schizophrenia

Maternal infections during pregnancy may increase the risk of psychiatric disorders in offspring. We recently demonstrated that activation of peroxisome proliferator-activate receptor-α (PPARα), with the clinically available agonist fenofibrate (FEN), attenuates the neurodevelopmental disturbances induced by maternal immune activation (MIA) in rat offspring. We hypothesized that fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By using the Bio-Plex Multiplex-Immunoassay-System, we measured cytokine/chemokine/growth factor levels in maternal serum and in the fetal brain of rats treated with fenofibrate, at 6 and 24 h after poly (I:C). We found that MIA induced time-dependent changes in the levels of several cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the maternal serum of the poly (I:C)/control (CTRL) group showed increased levels of (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1α), (ii) tumor necrosis factor-alpha (TNF-α), the monocyte chemoattractant protein-1 (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, interleukin 12p70 and MIP-1α levels were lower than in vehicle (veh)/CTRL group. Notably, MIP-1α, TNF-α, keratinocyte derived chemokine (GRO/KC), GM-CSF, and M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, suggesting the protective role of the PPARα agonist. PPARα might represent a therapeutic target to attenuate MIA-induced inflammation.

Inflammatory and Anti-Inflammatory Parameters in PCOS Patients Depending on Body Mass Index: A Case-Control Study.

it has been suggested that chronic low-grade inflammation plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). According to previous studies, it remains unclear which cytokines influence the development of this syndrome and whether their increase is associated with the presence of excess weight/obesity or is an independent factor. The aim of our research was to determine the parameters of chronic inflammation in women with PCOS in comparison with healthy women in the normal weight and the overweight subgroups. This case-control study included 44 patients with PCOS (19 women with a body mass index (BMI) < 25 kg/m² and 25 women with a BMI ≥ 25 kg/m²) and 45 women without symptoms of PCOS (22 women with a BMI < 25 kg/m² and 23 women with a BMI ≥ 25 kg/m²). Thirty-two cytokines were analyzed in the plasma of the participants using Immunology multiplex assay HCYTA-60K-PX48 (Merck Life Science, LLC, Germany). Cytokines: interleukin-1 receptor antagonist (IL-1 RA), IL-2, IL-6, IL-17 E, IL-17 A, IL-18, and macrophage inflammatory protein-1 alpha (MIP-1 α) were increased in women with PCOS compared to controls, both in lean and overweight/obese subgroups (p < 0.05). Moreover, only lean women with PCOS had higher levels of IL-1 alpha, IL-4, IL-9, IL-12, IL-13, IL-15, tumor necrosis factor (TNF- α) alpha and beta, soluble CD40 and its ligand (SCD40L), fractalkine (FKN), monocyte-chemotactic protein 3 (MCP-3), and MIP-1 β compared to the control group (p < 0.05). IL-22 was increased in the combined group of women with PCOS (lean and overweight/obese) compared to the control group (p = 0.012). Chronic low-grade inflammation is an independent factor affecting the occurrence of PCOS and does not depend on the presence of excess weight/obesity. For the first time, we obtained data on the increase in such inflammatory parameters as IL-9, MCP-3, and MIP-1α in women with PCOS.

Assessment of chemokines MIP-1α and MIP-1 βin Iraqi women with polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is reproductive, endocrine, and metabolic disorder affecting females. The pathology of PCOS is complicated and associated to chronic low-grade inflammation, this includes a disruption in pro-inflammatory factor production, leukocytosis, and endothelial cell dysfunction, also associated with high level of pro-inflammatory cytokines, chemokines and leukocyte count. In addition, PCOS is characterized by hormonal and immunological dysfunction. Inflammation of the ovary affects ovulation and induces or aggravates systemic inflammation. Macrophage inflammatory protein-1 (MIP-1), a pro-inflammatory chemokine, is crucial in the recruitment of inflammatory and immunological cells to the place of inflammation or infection, T- and B-lymphocytes, neutrophils, macrophages, mast cells, dendritic cells and natural killer cells are all capable of producing large amounts of MIP-1. The current study aimed to investigate the role of MIP-1α and MIP-1β in Iraqi patients with PCOS and their correlation with obesity and other demographic parameters. This study included two groups, 60 women with PCOS and 30 control women, conducted during the period from October 2022 to January 2023. The diagnosis of PCOS women was based on two out of three of the following diagnostic criteria (hyperandrogenism – oligo or anovulation – polycystic ovaries). MIP-1 alpha and Beta levels were determined by ELISA. The outcomes revealed that the group with PCOS showed significant increase in the level of MIP-1α (635.28 ±20.58) than in the control women, (571.20 ±25.92), (p&lt;0.05). Although there was an increase the level of MIP-1β in women with PCOS (191.85 ±17.54) than in the control group (165.31 ±11.01), the difference did not reach statistical significance. In conclusion, based on our findings, that MIP-1α and MIP-1β increased in PCOS cases, this may indicate that PCOS is low grade chronic inflammation.

The Protective Potential of Aronia melanocarpa L. Berry Extract against Cadmium-Induced Kidney Damage: A Study in an Animal Model of Human Environmental Exposure to This Toxic Element.

The impact of cadmium (Cd) on the function and structure of the kidney and the potential protective effect of an extract from Aronia melanocarpa L. berries were investigated in a rat model of low- and moderate-level environmental exposure to this heavy metal (1 and 5 mg Cd/kg feed for up to 24 months). The sensitive biomarkers of Cd-induced damage to the kidney tubules (N-acetyl-β-D-glucosaminidase (NAG), alkaline phosphatase (ALP), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) in the urine), clinically relevant early markers of glomerular damage (albumin in the urine and creatinine clearance), and other markers of the general functional status of this organ (urea, uric acid, and total protein in the serum and/or urine) and Cd concentration in the urine, were evaluated. The morphological structure of the kidney and inflammatory markers (chemerin, macrophage inflammatory protein 1 alpha (MIP1a), and Bcl2-associated X protein (Bax)) were also estimated. Low-level and moderate exposure to Cd led to damage to the function and structure of the kidney tubules and glomeruli. The co-administration of A. melanocarpa berry extract significantly protected against the injurious impact of this toxic element. In conclusion, even low-level, long-term exposure to Cd poses a risk of kidney damage, whereas an intake of Aronia berry products may effectively protect from this outcome.

Chemokine Levels among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality due to intense pulmonary inflammation. Enhanced chemokine-mediated leukocyte infiltration in lungs has been linked with unfavorable outcomes with respect to the disease. This cross-sectional study assessed the levels of chemokines among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 healthy controls using a customized Luminex human chemokine magnetic multiplex panel. The plasma levels of interferon-inducible protein (IP)-10 (568.5 ± 114.7 vs. 55.19 ± 5.85 pg/mL; p < 0.0001), macrophage inflammatory protein (MIP)-1 alpha (MIP-1A) (30.78 ± 2.81 vs. 18.16 ± 0.91 pg/mL; p < 0.0001), MIP-1B (36.63 ± 4.25 vs. 25.26 ± 1.51 pg/mL; p < 0.003), monocyte chemoattractant protein (MCP)-1 (1267 ± 309.5 vs. 390.0 ± 35.51 pg/mL; p < 0.0002), and monokine-induced gamma interferon (MIG) (28.96 ± 3.93 vs. 16.29 ± 1.69 pg/mL; p < 0.001), interleukin (IL)-8 (147.9 ± 21.57 vs. 84.63 ± 10.62 pg/mL; p < 0.004) were significantly higher in symptomatic patients than healthy controls. Likewise, the levels of IP-10 (247.6 ± 80.09 vs. 55.19 ± 5.85 pg/mL; p < 0.0002) and MCP-1 (650.7 ± 149 pg/mL vs. 390 ± 35.51 pg/mL; p < 0.02) were also significantly higher in asymptomatic patients compared to healthy controls. However, no differences were observed in the plasma levels of MIP-1A, MIP-1B, MIG, and IL-8 between asymptomatic patients and uninfected controls. Conversely, the mean plasma levels of regulated on activation normal T cell expressed and secreted (RANTES) (3039 ± 301.0 vs. 4390 ± 223 pg/mL; p < 0.001) and eotaxin (176.9 ± 30.20 vs. 296.2 ± 28.11 pg/mL; p < 0.01) were significantly lower in symptomatic MERS-CoV-infected patients compared to healthy controls. Likewise, the levels of eotaxin (162.7 ± 21.60 vs. 296.2 ± 28.11 pg/mL; p < 0.01) were also significantly lower in asymptomatic patients. Interestingly, the level of MCP-1 (2139 ± 548.2 vs. 776.5 ± 165.3 pg/mL; p < 0.004) was significantly higher in deceased symptomatic patients compared to recovered symptomatic patients. MCP-1 was the only chemokine associated with a higher risk of mortality. Symptomatic MERS-CoV-infected patients had a significant elevation of plasma chemokines and elevated MCP-1 levels were found to be associated with fatal outcomes.