IL-10 Ratio Research Articles

Low-Grade systemic inflammation is associated with domain-specific cognitive performance and cognitive decline in older adults: Data from the TUDA study

Studies examining the relationships between chronic inflammation, cognitive function and cognitive decline in older adults have yielded conflicting results. In a large cohort of older adults free from established dementia (n = 3270; 73.1 ± 7.9 years; 68.4% female), we evaluated the cross-sectional and longitudinal relationships between serum cytokines (IL-6, IL-10, TNF-α) and both global and domain-specific cognitive performance (Repeatable Battery for Assessment of Neuropsychological Status [RBANS]). Higher IL-6 (OR: 1.33; 1.06, 1.66, p = 0.01), TNF-α (OR: 1.35; 1.09, 1.67, p = 0.01) and IL-6:IL-10 Ratio (OR: 1.43; 1.17, 1.74, p = 0.001) were cross-sectionally associated with impaired global RBANS performance. For specific cognitive domains, greatest effect sizes were observed between higher TNF-α levels and poorer visual-spatial and attention performance. In a subset of participants (n = 725; 69.8 ± 5.5 years; 67.0% female) with repeat assessment performed at a median of 5.4 years, only higher baseline IL-6:IL-10 ratio was associated with impaired incident overall, immediate memory and visual-spatial performance. Associations were stronger in females, but not modified by age or APOE genotype.

Efficacy and Safety of BTK Inhibitors in Vitreoretinal Lymphoma: A Single-Center, Retrospective Analysis of 24 Patients

Background: Vitreoretinal lymphoma (VRL) is a special subtype of rare central nervous system lymphoma (PCNSL). Most of the pathologic types are diffuse large B-cell lymphoma of non-germinal central origin. Currently, the optimal treatment strategy for VRL is not clear, and the traditional treatment usually includes about 20 repeated intravitreal injections of low doses of methotrexate or intraocular local radiotherapy. Eventually, however, 60-90% of VRL will progress to PCNSL. Therefore, CNS prophylaxis of VRL patients is very important. A previous prospective clinical study of our research group (including 10 VRL patients) confirmed that single-drug BTK inhibitors can replace repeated intravitreal injection of low doses of methotrexate, with rapid effect, high safety, and certain value in preventing CNS progression. Methods: In order to further clarify the efficacy and safety of BTK inhibitors in VRL patients, we included 24 VRL patients who were consecutively admitted to the Hematology Department of Beijing Tongren Hospital from May 2020 to December 2022, and retrospectively analyzed their clinical features, treatment methods, treatment outcomes, survival status and treatment-related adverse reactions. Results: Of the 24 patients, 14 were female and 10 were male, with a median age of 62 years old (36-75). There were 18 patients with primary VRL (PVRL) and 6 patients with secondary VRL (SVRL) to PCNSL. The IL-10 in aqueous humor/vitreous fluid at baseline was significantly increased in all patients (362.1±89.5pg/mL), and the IL-10/IL-6 ratio was greater than 1. Except for one patient with both uncontrolled PCNSL and VRL, the other 23 VRL patients showed no evidence of CNS involvement by brain MRI and cerebrospinal fluid detection. All 24 patients were treated with a BTK inhibitor (Zanubrutinib 160mg bid, or Orelabrutinib 150mg qd), of whom, 9 VRL patients were also treated with intravitreal methotrexate injection (0.4mg/ time, weekly ×12 times → monthly ×9 times) concurrently, and the remaining 15 patients did not receive any antitumor therapy other than BTK inhibitors. After 1 month of treatment with BTK inhibitors, the efficacy was evaluated by slit lamp microscope, optical coherence tomography (OCT), and aqueous humor cytokines. 21 patients achieved CR (87.5%), 2 PR (8.3%), and 1 PD (progression of CNS lesion but improvement of intraocular disease). The IL-10/IL-6 levels in aqueous humor were lower than 1 in all 24 patients 1 month after treatment, and the IL-10 levels in aqueous humor were slightly higher than the normal range in two patients. The median duration of BTK inhibitors use was 10 months (1.5-23.0 months). At a median follow-up of 17 months (5.4-31.5 months), 15 patients (62.5%) developed disease progression, including 11 patients (45.8%) with CNS progression and 4 patients (16.7%) with intraocular recurrence. The median progression-free survival (PFS) time was 11.9 months, and the median overall survival (OS) time was not reached. The 1-year and 2-year PFS rates were 34% and 26%, and the 1-year and 2-year OS rates were 96% and 82%, respectively. The recurrence rate was 33.3% in the combined treatment group and 80.0% in the BTK inhibitors monotherapy group. A total of three patients died, all due to CNS progression. BTK inhibitors were generally well tolerated in VRL patients, with no adverse reactions that led to treatment discontinuation. 4 patients had grade 1-2 hypertension (16.7%), 1 patient had grade 1 hypotension (4.2%), 2 patients had grade 1 joint pain (8.5%), and 6 patients had grade 1 subcutaneous hemorrhage and ecchymosis (25.0%). Four patients developed COVID-19 infection while taking the drug and the drug was suspended. All four patients recovered from COVID-19 infection within 2 weeks and did not develop significant pneumonia. Conclusion: This is the largest report regarding the use of BTK inhibitors in VRL patients. BTK inhibitor has a rapid local control effect on VRL and is well tolerated. However, BTK inhibitors monotherapy has unsatisfied preventive effect on the CNS, and it is still necessary to explore the value of combinational therapy, such as combined BTK inhibitors and high-dose methotrexate.

Cholesterol crystals as the main trigger of interleukin-6 production through innate inflammation in human spontaneously ruptured aortic plaques

Abstract Aim Cholesterol crystals (CCs) may provoke innate inflammation in experimental and animal model, however, whether CCs are bystanders or play central role for plaque rupture is unknown. This study aimed to clarify whether CCs was the main trigger of innate inflammation in human spontaneously ruptured aortic plaques (SRAPs). Methods This study included 260 SRAPs collected during non-obstructive general angioscopy (NOGA) from 126 patients with having or suspected CAD. Interleukin (IL)-6 levels in SRAPs were measured. IL-6 level at the Valsalva sinus, and femoral or brachial arteries were measured. IL-6 ratios, IL-6 level in SRAPs and arteries divided by IL-6 level at the Valsalva sinus at the beginning of aorta, were calculated. The number of CCs were counted in sampled blood. The correlation between the count of CCs and IL-6 levels in SRAPs and that between the counts of CCs and IL-6 ratios in SRAPs were analyzed. Results IL-6 ratios of the brachial and femoral arteries were 1.06 (95% CI, 0.99–1.20) and 1.11 (95% CI, 1.04–1.20), respectively. IL-6 ratio in SRAPs was 1.10 [1.00, 1.26]. (median [IQR]). CCs were detected in 94 of 260 SRAPs (36%). The count of CCs was 11,590 (95% CI: 2,386–30,113] per 10 mL in CCs positive samples. There was a moderate correlation between the counts of CCs and IL-6 ratios in SRAPs (r=0.496, r<0.0001)(Fig. 1), whereas there was no correlation between the count of CCs and IL-6 levels in SRAPs.(Fig. 2) Conclusions By the in-situ study, CC might be the main trigger of IL-6 through innate inflammation in human SRAPs.Fig 1Fig 2

The Geriatric Nutritional Risk Index (GNRI) to IL-6 ratio as a Predictor of Mortality in a Long-Term Follow-Up of Hemodialysis Patients

The Geriatric Nutritional Risk Index (GNRI) to IL-6 ratio as a Predictor of Mortality in a Long-Term Follow-Up of Hemodialysis Patients

Effect of lactoferrin in oral nutrition supplement (ONS) towards IL-6 and IL-10 in failure to thrive children with infection

Background: Growth failure due to infection in children is a major health problem throughout the world. It provokes a systemic immune response, with increased interleukin (IL)-6 and reduced IL-10. Lactoferrin (Lf) is a multifunctional iron-binding protein that can be found in whey protein inside formula milk such as oral nutrition supplement (ONS), which can upregulate anti-inflammatory cytokines (IL-10) and modulate pro-inflammatory cytokines. This study investigates the effect of Lf supplementation in ONS on IL-6 and IL-10 levels in children with failure to thrive and infection. Methods: We performed a quasi-experimental pre- and post-study in children aged 12–60 months old with failure to thrive due to infectious illness. The subjects received 400 ml of oral nutritional supplements (ONS, 1 ml equivalent to 1 kcal) each day for 90 days, and their parents received dietary advice and medication based on the underlying illness. Blood was drawn to measure IL-6 and IL-10 before and after the intervention. Results: There were 75 subjects recruited and divided into group-1 and group-2 based on age. The incidence of undernutrition was 37.33%. Lf in ONS intervention improved body weight and body length. Lf also reduced IL-6, although there was not a significant difference before and after the intervention. However, the IL-6 reduction was significantly higher in subjects with undernutrition compared with subjects with weight faltering. Pre-intervention IL-6 levels were higher in children with stunting than in children with normal stature. There was a greater change in IL-6 in children with severe stunting than in children with normal stature or stunting. IL-10 was significantly reduced after the intervention. Conclusions: In addition to improving body weight and length, Lf supplementation in ONS improved immune response homeostasis by balancing IL-6 and IL-10 levels and by improving the IL-6/IL-10 ratio. ClinicalTrials.gov number ID: NCT05289674, dated May 3rd 2022.

The fluctuations of expression profiles of critical genes in the miRNA maturation process and pro-and anti-inflammatory cytokines in the pathogenesis and progression of multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. It was assessed the expression patterns of the genes (Drosha, Pasha(DGCR8), and Dicer) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-β, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-β cytokines are consistent with the progression of the disease. Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS.

Partner relationship quality and IL-6:IL-10 trajectories from pregnancy to a year after-birth

BackgroundInflammatory activity during pregnancy and the postpartum period shifts systematically due to pregnancy progression, delivery, and postpartum recovery. Factors that deregulate inflammatory activity increase the risk for adverse pregnancy outcomes and slower postpartum recovery. The IL-6:IL-10 or TNF-α:IL-10 ratio is potentially one way to capture peripheral inflammatory regulation; higher values indicate that anti-inflammatory IL-10 is less effective at regulating pro-inflammatory TNF-α or IL-6, skewing towards maladaptive pro-inflammatory profiles. Associations between partner relationship quality and IL-6:IL-10 or TNF-α:IL-10 trajectories during pregnancy and the postpartum period have not been assessed. The purpose of this study was to test whether partner relationship quality (support, conflict) is associated with attenuated IL-6, IL-10, TNF-α, TNF-α:IL-10 or IL-6:IL-10 trajectories from the third trimester to the postpartum period. MethodsA sample of 162 women from the Healthy Babies Before Birth study reported on partner relationship quality (support and conflict) using the Social Support Effectiveness Questionnaire during the third trimester. Plasma samples were collected in the third trimester and at 1-, 6- and 12-months postpartum, and assayed for TNF-α, IL-6 and IL-10. Associations between both indicators of relationship quality (support and conflict) and TNF-α, IL-6, IL-10, IL-6:IL-10, TNF-α:IL-10 trajectories were tested using multi-level modelling, controlling for sociodemographic, pregnancy and health variables. ResultsPartner support interacted with time to predict IL-6:IL-10 trajectories, linear: b = -0.176, SE = 0.067, p =.010, quadratic: b = 0.012, SE = 0.005, p =.009. Lower partner support was associated with steeper increases in IL-6:IL-10 from the third trimester to 6 months postpartum, followed by steeper decreases in IL-6:IL-10 from 6 months postpartum to a year after birth. Partner conflict was not associated with IL-6:IL-10 levels at study entry, b = 0.233, SE = 0.219, p =.290, or over time, p’s > 0.782. Neither indicator of partner relationship quality was associated with TNF-α, IL-6, IL-10, or TNF-α:IL-10 trajectories, p’s > 0.205. ConclusionLower partner support may be associated with reduced moderation of IL-6 by IL-10 between pregnancy and a year postpartum, with possible consequences for maternal health and well-being.

Assessment of tissue levels of miR-146a and proinflammatory cytokines in experimental cerebral toxoplasmosis following atovaquone and clindamycin treatment: An in vivo study

BackgroundDespite recent advances for treating cerebral toxoplasmosis (CT), monitoring the parasite burden and treatment response is still challenging. miRNAs are small non-coding RNAs with regulatory functions that can be used in diagnosis and treatment monitoring. We investigated the changes in miR-146a, BAG-1 gene, IL-6, and IL-10 tissue levels in the brain of BALB/c mice with chronic CT caused by the PRU strain of T. gondii following anti-parasitic and antibiotic treatment. MethodFifty-three 6-to 8-week-old BALB/c mice were infected using intraperitoneal inoculation of cerebral cysts of T. gondii PRU strain and then divided into five groups as follows: group 1 included mice treated with 100 mg/kg/d Atovaquone (AT), group 2 included mice treated with 400 mg/kg/d clindamycin (CL), group 3 included mice treated with combination therapy (AT + CL), group 4 included infected untreated mice as a positive control (PC), and; group 5 included uninfected untreated mice as negative control (NC). After the completion of the treatment course, tissue level of mir-146a, miR-155, BAG-1 gene, IL-6, and IL-10 was investigated with real-time polymerase chain reaction. The IL-6/IL-10 ratio was calculated as an indicator of immune response. Moreover, brain cyst numbers were counted on autopsy samples. ResultsmiR-146a, IL-6, IL-10, and BAG-1 genes were expressed in PC, but not in the NC group; miR-146a, IL-6, IL-10, and BAG-1 gene expression were significantly lower in AT, CL, and AT + CL compared with PC. MiR-146a and BAG-1 levels in AT and CL were not different statistically, however, they both had lower levels compared to AT + CL (P < 0.01). There was no difference in the expression of IL-6 and IL-10 between treatment groups. BAG-1 expression was significantly lower in AT, than in CL and AT + CL (P < 0.0089 and < 0.002, respectively). The PC group showed a higher ratio of IL-6/IL-10, although this increase was not statistically significant. It is noteworthy that the treatment with AT reduced this ratio; in the inter-group comparison, this ratio showed a decrease in the AT and AT + CL compared to the PC. The number of brain tissue cysts was significantly lower in AT, CL, and AT + CL, than in PC (p < 0.0001). AT had significantly lower brain cysts than CL and AT + CL (P < 0.0001). ConclusionIt seems that the factors studied in the current research (microRNA and cytokines) are a suitable index for evaluating the response to antiparasitic and antibiotic treatment. However, more studies should be conducted in the future to confirm our findings.

Influence of Porphyra-derived polysaccharides and oligosaccharides on attenuating food allergy and modulating enteric microflora in mice

ABSTRACT Recently, there have been reports on the immunomodulatory properties of polysaccharides (PP), oligosaccharides (PO), and mixtures of PO/PP derived from Porphyra. To explore their potential in alleviating allergic responses and enteric dysbiosis, this study delved deeper into their effects using a murine model of food allergy. Daily administration of Porphyra samples mitigated allergic diarrhea, enteritis, and allergen-specific IgE production. Moreover, Porphyra samples exerted a significant reduction in the secretion of IL-2, IL-4, IFN-γ, and IL-17A, along with an elevation in the IL-10/IL-4 ratio in splenocytes upon allergen stimulation. Similarly, expression of IL-4 and IFN-γ in the duodenum was suppressed. Notably, allergic mice displayed a distinct fecal microflora profile compared to that of normal mice. Interestingly, PP and PO treatments exhibited different effects on improving enteric dysbiosis. These findings collectively suggest the potential of PP and PO as functional food candidates for the management of allergic enteritis and dysbiosis.

Relationship of Cytokine Status Parameters with the Lipid Peroxidation-Antioxidant Defense System in Obese Adolescents

The aim of this study was to identify the relationships between cytokine status, lipid peroxidation (LPO) products, and total antioxidant activity (TAA) in obese adolescent boys and girls. Methods and Results: The study included 29 boys and 33 girls with an established diagnosis of exogenous-constitutional obesity of the first degree. Twenty-eight healthy adolescent boys and 24 adolescent girls made up control groups. The concentration of cytokines (IL-6, IL-8, IL-4, and IL-10) was assessed by enzyme immunoassay. The content of LPO products (conjugated dienes [CDs], ketodienes and conjugated trienes [KD-CT], Schiff bases [SB], thiobarbituric acid reactants [TBARs], total antioxidant activity (TAA) was evaluated. Spectrophotometric methods were used. The data obtained indicated a statistically significant increase in the level of IL-6 (P=0.018) and the IL-6/IL10 ratio (P=0.033) in obese boys, compared with the control. There was also an increase in the content of LPO products in this group relative to the control group: KD-CT (P=0.043) and SB (P=0.021). In the group of obese girls, there was an increase in IL-6 values (P=0.018), a decrease in IL-4 (P=0.040), and an increase in CDs (P=0.035) and KD-CT (P=0.044). The following correlations were found in the control group of boys: CDs‒KD-CT (r=0.91; P=0.001), TBARS‒IL-8 (r=0.73; P=0.027), and SB‒IL-4 (r=0.79; P=0.011); there were no statistically significant correlations between study parameters in obese boys. The following correlations were recorded in the girls of the control group: CDs‒KD-CT (r=0.99; P&lt;0.0001), TAA‒IL-10 (r=-0.80; P=0.033), TAA‒IL-4 (r=-0.78; P=0.040); in obese girls, it was SB‒IL-4 (r=-0.67; P=0.048). Conclusion: Data analysis showed high activity of proinflammatory cytokines and LPO products in obese adolescents, regardless of gender, with a reduced concentration of anti-inflammatory factors and correlations between parameters of inflammation and OS in girls. An important component of the pathogenetic approach in treating obesity should be the control of these parameters.

Th1/Th2 cytokine profile in patients with acute and chronic calculus cholecystitis.

Relatively little is known about the relationship between Th1/Th2 cytokines and calculus cholecystitis (CC). The purpose of this study was to investigate the correlation between serum Th1 and Th2 cytokine expression and CC, including both acute and chronic cases. In total, 102 patients with chronic calculous cholecystitis (CCC), 64 patients with acute calculous cholecystitis (ACC), and 55 healthy controls (HCs) were recruited for the study. Serum concentration of Th1 (IL-2, TNF-α, IFN-γ) and Th2 cytokines (IL-4, IL-6, IL-10) was measured at admission and on the fifth day after cholecystectomy using flow cytometry. In addition, the ratio of IL-6/IL-10 was calculated. Correlation of the corresponding factors was then analysed, and univariate and multivariate Cox regression analyses were performed to identify independent markers of ACC severity. Compared to HCs, CCC patients exhibited significantly elevated expression levels of IL-6 and IL-10, while ACC patients demonstrated higher expression of IL-2, TNF-α, and IL-6/ IL-10 in addition to IL-6, and IL-10. In ACC patients, there was a strong positive correlation between IL-6 and IL-10 concentration, the expression of IL-2 was observed to positively correlate with serum ALT and AST concentration, and TNF-α expression positively correlated with the duration of hospitalization. Moreover, patients with moderate-to-severe ACC presented with higher expression of IL-10 compared to those with mild ACC. Cox regression analysis confirmed that IL-10 and IL-6 were independent factors for the severity of ACC. Following surgery, the levels of IL-6 and IL-6/IL-10 significantly decreased but did not fully return to baseline levels in ACC patients. Our study reveals atypical Th1/Th2 cytokine expression profiles in patients with acute and chronic CC, and further highlights the significant potential of these cytokines, particularly IL-6 and IL-10, in assessing the severity and progression of CC.

Specific dysregulation of inflammatory and anti-inflammatory cytokine responses in pregnant women with COVID-19 infections

Context: Owing to its extensive inflammation, COVID-19 infection may have a specific response in the anti-inflammatory milieu of pregnancy. Aims: To analyze the lacking evidence of systemic inflammatory and anti-inflammatory cytokine responses of pregnant women with COVID-19 infection compared to normal pregnancies. Methods: This case-control study was performed on third-trimester symptomatic COVID-19 pregnant women compared with normal pregnancies without other significant inflammation risks. A between-group analysis was conducted to assess the inflammatory, and anti-inflammatory cytokines and chemokines. Through a comparison and correlation analysis, we detected differences between cytokines in the COVID-19 group based on the severity of the infection. Results: Pregnant women with COVID-19 had higher procalcitonin levels (p&lt;0.01), IL-6 (p=0.05), TNF-, IFN-γ/IL-4 ratio (p&lt;0.01), and lower IL-4 (p&lt;0.05), implying a higher proinflammatory cytokine imbalance in this group compared with normal pregnancies. White blood cells (p&lt;0.05; r=0.345), and IL-17 (p&lt;0.05; r=0.328) had weak positive correlation, while CRP (p&lt;0.01; r=0.484), and IL-6 (p&lt;0.01; r=0.41), had moderate positive correlation with COVID-19 severity during pregnancy. Conclusions: COVID-19 infections provide a unique non-dominance of the anti-inflammatory response in pregnant women, as indicated by a lower response of Th2, which may counteract the Th1 response. These cytokine dysregulations may disturb the viral defense mechanism, leading to a proinflammatory condition as shown by higher TNF-, IL-6, and IFN-/IL-4 ratios. Some inflammatory markers have a positive correlation with COVID-19 severity (WBC, CRP, IL-6, and IL-17), suggesting their potential roles as severity markers during pregnancy.

Analysis of MCP-1 Levels and TNF-alfa /Il-10 Ratio in First Degree Relatives (FDR) Type 2 Diabetes Mellitus Subjects with High Fat Diet Treatment

Type 2 diabetes mellitus is a chronic metabolic disease, which involves a variety of pathogenic processes. Overall these processes result in loss of mass and/or function of pancreatic-cells which is manifested as hyperglycemia. The influence of familial factors appears to be involved in the initiation and development of T2DM through both genetic and non-genetic factors. In the same family environment as patients with diabetes, first-degree relatives of patients with diabetes show a 30-70% increased risk of developing diabetes. Insulin resistance and cell dysfunction have been identified in individuals with a family history of diabetes, even before the onset of T2DM symptoms. Monocyte chemoattractant protein-1 (MCP-1) is a CC-chemokine with an attractant effect on monocytes, memory T cells and basophils. Expression of adipose tissue MCP-1 and circulating levels were positively correlated with adiposity. Larger adipocytes are associated with insulin resistance. This study aims to determine the changes in MCP-1 expression on monocytes before and after treatment with a high-fat diet for five days. The results showed that there was a change in inflammatory activity which was indicated by a high ratio of TNF-alfa/IL – 10 in the FDR group so that it could increase MCP-1 activity. However, there was no relationship between serum MCP-1 levels and the percentage of CD14+CD16+ monocytes in both groups.

Elevated interleukin-10 levels in patients with ocular toxoplasmosis.

In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common pathology of uveitis in older adults. The high level of interleukin (IL)-10 and an IL-10/IL-6 ratio higher than 1 (>1.0) are helpful parameters to diagnose ocular lymphoma. In this study, we used aqueous humor samples to detect 4 cases of ocular toxoplasmosis in patients with high levels of IL-10 and an IL-10/IL-6 ratio higher than 1. Our results show that ocular toxoplasmosis may be associated with increased cytokine levels in aqueous humor.

The features of the production of interleukins-4, -8, -10 and -18 in normal third trimester pregnancy

The serum level of ILL-4, -8, -10, -18 has been studied in 32 healthy women with uncomplicated pregnancy in comparison with nonpregnant women. It has been shown that the decreased production of ILL-4, -8, -10 and IL-8/IL-18 ratio, but increased production of IL-18 and IL-18/IL-10 ratio.

Effect of lactoferrin in oral nutrition supplement (ONS) towards IL-6 and IL-10 in failure to thrive children with infection

Background: Growth failure due to infection in children is a major health problem throughout the world. It provokes a systemic immune response, with increased interleukin (IL)-6 and reduced IL-10. Lactoferrin (Lf) is a multifunctional iron-binding protein that can be found in whey protein inside formula milk such as oral nutrition supplement (ONS), which can upregulate anti-inflammatory cytokines (IL-10) and modulate pro-inflammatory cytokines. This study investigates the effect of Lf supplementation in ONS on IL-6 and IL-10 levels in children with failure to thrive and infection. Methods: We performed a quasi-experimental pre- and post-study in children aged 12–60 months old with failure to thrive due to infectious illness. The subjects received 400 ml of oral nutritional supplements (ONS, 1 ml equivalent to 1 kcal) each day for 90 days, and their parents received dietary advice and medication based on the underlying illness. Blood was drawn to measure IL-6 and IL-10 before and after the intervention. Results: There were 75 subjects recruited and divided into group-1 and group-2 based on age. The incidence of undernutrition was 37.33%. Lf in ONS intervention improved body weight and body length. Lf also reduced IL-6, although there was not a significant difference before and after the intervention. However, the IL-6 reduction was significantly higher in subjects with undernutrition compared with subjects with weight faltering. Pre-intervention IL-6 levels were higher in children with stunting than in children with normal stature. There was a greater change in IL-6 in children with severe stunting than in children with normal stature or stunting. IL-10 was significantly reduced after the intervention. Conclusions: In addition to improving body weight and length, Lf supplementation in ONS improved immune response homeostasis by balancing IL-6 and IL-10 levels and by improving the IL-6/IL-10 ratio. ClinicalTrials.gov number ID: NCT05289674, dated May 3rd 2022.

Association among inflammaging, body composition, physical activity, and physical function tests in physically active women.

Inflammaging is a phenomenon that has been associated with the development and progression of sarcopenia and frailty syndrome. According to the literature, on the one side, the increase in body fat is associated with a systemic pro-inflammatory status, which consequently favors inflammaging, and on the other side, the regular practice of physical exercise can mitigate the development of this scenario. Therefore, here, we aimed to evaluate the association between inflammaging and physical factors, both body and functional, in a group of physically active older women. Seventy older women (mean age 72.66 ± 6.17 years) participated in this observational cross-sectional and were separated into the eutrophic, overweight, and obese groups. It was assessed: by bioimpedance-body fat percentage (Fat%) and total (Fat kg), skeletal muscle mass (muscle), and free fat mass both in percentage (FFM%) and total (FFMkg); by the International Physical Activity Questionnaire (IPAQ)-the time of moderate-intensity physical activity per week; by physical tests-handgrip (HG), sit-up-stand-on-the-chair in 5 repetitions (Sit-up) and vertical squat jump test (SJ); in addition to the determination of serum cytokine concentration (IL-6, TNF-α, IL-10, and IL-8), and also body mass index (BMI) and calf circumference (Calf). Higher FFM% and lower body fat (both kg and %) were found in the eutrophic group than in the other groups. The eutrophic group also performed more weekly physical activity, jumped higher, and presented not only higher serum IL-6 concentration but also an increased ratio of IL-10/IL-6, IL-10/TNF-α, IL-10/IL-8 as compared to the values found in the overweight group. The obese group presented higher body fat (kg and %) and lower FFM% than the other groups and also higher serum IL-6 concentration than the overweight group. Interestingly, several significant negative and positive correlations between body composition, physical tests, and serum cytokine concentrations were found in the eutrophic and obese groups. While the eutrophic older women group showed a remarkable regulation of the systemic inflammatory status with positive associations in the physical parameters assessed, the overweight and obese groups presented impairment regulations of the inflammaging, which could be related to less weekly physical activity and higher body fat.

Keratic precipitates morphology in vitreoretinal lymphoma evaluated with in-vivo confocal microscopy

A 51-year-old female patient presented to our department with a one-year history of bilateral blurred vision with floaters. Ocular examination showed bilateral vitritis with a moderate haze which was more accentuated and prominent at the periphery in the right eye (OD) (figure 1 A, asterisks). Spectral-domain optical coherence tomography (SD-OCT) showed numerous pigment epithelial detachment (figure B, white arrows), with a lumpy-bumpy choroid. The diagnosis of vitreoretinal lymphoma (VRL) was suspected and confirmed histologically by the presence of atypical lymphocytes in the vitreous samples and an elevated Interleukin (IL)-10 to IL-6 ratio. In addition to those posterior segment manifestations, slit-lamp examination of the OD showed central stellate granulomatous keratic precipitates (KPs) (figure C). On in-vivo confocal microscopy (IVCM), those infiltrating KPs appeared as a hyperreflective deposit at the level of the corneal endothelium with a dendritic shape, and were interconnected by multiple thin and fibrillar pseudopodia in a comet-like appearance (figure D, yellow arrows), which is a highly suggestive pattern of KPs of VRL associated anterior uveitis when the latter is unusually granulomatous.

Effect of dihydroquercetin on the toxic properties of nickel nanoparticles

Dihydroquercetin (3,5,7,3',4'-pentahydroxy-flavanone) is known for its powerful antioxidant, organ-protective, and antiinflammatory activities that can be applied to heavy-metal intoxication. The present research objective was to evaluate the possible protective potential of dietary dihydroquercetin in a rat model of subacute (92 days) intoxication with nickel nanoparticles.&#x0D; The experiment involved five groups of twelve male Wistar rats in each. Group 1 served as control. Other groups received nickel nanoparticles as part of their diet. Groups 2 and 4 received nickel nanoparticles with an average diameter of 53.7 nm (NiNP1), while groups 3 and 5 were fed with nanoparticles with an average diameter of 70.9 nm (NiNP2). The dose was calculated as 10 mg/kg b.w. Groups 4 and 5 also received 23 mg/kg b.w. of water-soluble stabilized dihydroquercetin with drinking water. &#x0D; After the dihydroquercetin treatment, the group that consumed 53.7 nm nickel nanoparticles demonstrated lower blood serum glucose, triglycerides, low-density lipoprotein cholesterol, and creatinine. Dihydroquercetin prevented the increase in total protein and albumin fraction associated with nickel nanoparticles intake. The experimental rats also demonstrated lower levels of pro-inflammatory cytokines IL-1β, IL-4, IL-6, and IL-17A, as well as a lower relative spleen weight after the treatment. In the group exposed to 53.7 nm nickel nanoparticles, the dihydroquercetin treatment increased the ratio of cytokines IL-10/IL-17A and decreased the level of circulating FABP2 protein, which is a biomarker of increased intestinal barrier permeability. In the group that received 70.9 nm nickel nanoparticles, the dihydroquercetin treatment inhibited the expression of the fibrogenic Timp3 gene in the liver. In the group that received 53.7 nm nickel nanoparticles, dihydroquercetin partially improved the violated morphology indexes in liver and kidney tissue. However, dihydroquercetin restored neither the content of reduced glutathione in the liver nor the indicators of selenium safety, which were suppressed under the effect of nickel nanoparticles. Moreover, the treatment failed to restore the low locomotor activity in the elevated plus maze test.&#x0D; Dihydroquercetin treatment showed some signs of detoxication and anti-inflammation in rats subjected to nickel nanoparticles. However, additional preclinical studies are necessary to substantiate its prophylactic potential in cases of exposure to nanoparticles of nickel and other heavy metals.

Clinicopathological analysis and specific discriminating markers of interleukin detection in cerebrospinal fluid with primary central nervous system lymphoma: results from a retrospective study.

Primary central nervous system lymphoma (PCNSL) is special extranodal malignant non-Hodgkin lymphomas. This study analyzed clinical features and prognostic factors of PCNSL and evaluated the difference of interleukin (IL) concentrations incerebrospinal fluid (CSF) between PCNSL and systemic non-Hodgkin lymphoma (sNHL). Patients consecutive newly diagnosed with PCNSL were recruited, the demographic and clinicopathological data were retrospectively analyzed, and the potential prognostic factors for overall survival (OS) were identified with survival analysis. 27 patients with PCNSL and 21 patients with sNHL collected CSF IL-5, IL-6, and IL-10 concentrations at diagnosis. The difference in interleukin (IL) concentrations in two diseases was analyzed to evaluate the value of IL concentrations. A total of 64 patients with PCNSL were enrolled, the median age was 54.50years (range 16-85years); male: female ratio was 1.91. Headache was the most common complaint symptom involved in 42.19% (27/64) of patients. Diffuse large B-cell lymphoma (DLBCL) accounted for 89.06% (57/64) of patients; other uncommon types accounted for 3.13% (2/64). In prognostic analysis, multiple lesions and Ki67 ≥ 75% expression exhibited a worse prognosis(P = 0.041), and patients with autologous hematopoietic stem cell transplantation (auto-HSCT) treatment presented superior OS (P < 0.05). In multivariate analysis, BCL2 expression was revealed as an unfavorable prognostic marker, and auto-HSCT was revealed as a favorable prognostic marker. CSF IL-10 concentration in patients with PCNSL was significantly higher than sNHL (P = 0.000) and excluded other histopathology of NHL; IL-10 value was still significantly different between DLBCL of PCNSL and sDLBCL (P = 0.003). In ROC curve analysis, the cutoff value of IL-10 was 0.43pg/mL for the diagnosis value of PCNSL, sensitivity was 96.3%, specificity was 66.67%, and AUC was 0.84 (0.71-0.96). Although IL-6 concentration did not differ in the two groups, IL-10/IL-6 ratio was meaningful, with a cutoff value of 0.21, sensitivity of 81.48%, specificity of 80.95%, and AUC of 0.83 (0.71-0.95). This study highlights the characteristics of patients with PCNSL, potential prognostic makers also have been explained. CSF interleukin (IL) concentrations revealed IL-10 levels, and IL-10/IL-6 ratio may represent a useful biomarker in the differential diagnosis of PCNSL and sNHL.