Significant Difference In IL-1β Research Articles

Study the Effect of IL-1beta on Thyroid Hormones Levels in Women with Hypo- and Hyperthyroidism in the City of Ramadi

Thyroiditis is a medical condition of particular concern due to its diverse causes, including autoimmune factors, drug-induced inflammatory causes or fibrotic process, the most common of which is thyroiditis and includes hypothyroidism and hyperthyroidism. The study aimed to measure interleukin 1 beta (IL-1β) and compare it with the studied groups and the hormones TSH, T3, T4 and their relationship with IL-1β. The study included investigating the relationship between IL-1β and thyroid patients in females aged between (18-60) in the city of Ramadi as well as knowing the relationship between thyroid hormones (TSH, T4, T3) and IL-1β. 45 samples were collected from Ramadi Teaching Hospital. The current study showed that there was a significant increase in the level of IL-1β compared to the control group in hypothyroid patients at a significant level (P≤0.05), which was (2.3497ng/dl). There were no significant differences in the level of IL-1β in patients with hyperthyroidism at a significant level (P≤0.05), which was (ng/dl 2.0690) compared to the control group. The study showed that there is an inverse relationship between TSH and IL-1β (0.858) and a positive relationship between T4 and IL-1β (0.809) .We conclude from the study that interleukin 1 beta (IL-1β) has an effect on the thyroid gland, especially hypothyroidism, as it showed a highly significant increase in IL-1β in patients with hypothyroidism and no significant differences in IL-1β, as IL-1β affects thyroid hormones

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell’s median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Selective Upregulation of Interleukin 1 Receptor Antagonist and Interleukin-8 in Fuchs' Endothelial Corneal Dystrophy with Accompanying Cataract.

(1) Background: Patients with Fuchs' endothelial corneal dystrophy (FECD) may have coexisting cataracts and, therefore, may require a cataract surgery, which poses challenges due to potential endothelial cell damage. FECD is a degenerative eye disease of unclear etiology, with inflammatory cytokines maybe playing an important role in its development and progression. The present study aimed to investigate the cytokine profile in the aqueous humor of FECD eyes with cataract. (2) Methods: Fifty-two patients were included in the study, 26 with FECD + cataract and 26 with cataract as a control group. Samples of the aqueous humor were analyzed for pro- and anti-inflammatory cytokines using a Bio-Plex 200 system. (3) Results: Interleukin 1 receptor antagonist (IL-1Ra) and interleukin IL-8 levels were significantly higher in the aqueous humor of FECD + cataract patients compared to the control/cataract group. Moreover, the levels of anti-inflammatory IL-10 showed a strong trend to be higher in the FECD + cataract group compared to the control group. In contrast, there were no statistically significant differences in IL-1β, IL-6, IL-4, IL-10, IL-13, IL-17A, and tumor necrosis factor TNF-α between the groups. (4) Conclusions: Presented research contributes to a better understanding of FECD pathogenesis. Elevated levels of IL-1Ra and IL-8 may serve as a defense mechanism in people with FECD and coexisting cataract.

Proinflammatory cytokines IL-6, IL-1β, TNF-α in infective endocarditis

Aim. To study the features of macrophages in the tissues of resected valves in operated patients with infective endocarditis (IE), their significance and interaction with inflammatory markers to improve the effectiveness of IE diagnosis. Materials and methods. Prospectively the research included 25 adult patients with active IE (Duke criteria 2015) and 24 patients with heart defects without IE, hospitalized in a cardiosurgical hospital in Moscow (2021–2022). A standard laboratory and instrumental examination was carried out for the diagnosis of IE, including etiological diagnosis with microbiological and molecular biological methods, and echocardiographic examination of heart. Additionally, the neutrophil-to-lymphocyte ratio (NLR) was calculated. The study of macrophages was carried out in the tissues of resected valves with the determination of the expression of pro- and anti-inflammatory cytokine genes, macrophage markers (CD 68+) using real-time PCR. Results. Increased expression of proinflammatory cytokines IL-1β, TNF-α and IL-6 was revealed in the group of operated patients with IE with significant differences in IL-1β (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p0.05) and IL-6 (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p0.05) and IL-6 (CI [IQR] 0.00338 [0.00066–0.01674] vs 0.00054 [0.00044–0.00378]; p0.05). The expression of anti-inflammatory cytokines in valve tissues prevailed in the control group without significant differences from patients with IE. The macrophage marker CD 68+ was revealed in all examined patients with a significant quantitative predominance in the group of patients with IE. There were no differences in the expression of pro- and anti-inflammatory cytokines depending on the presence of embolic events, intracardiac complications, etiological affiliation to S. aureus, as well as hospital mortality and combined endpoint (death from all causes or recurrence of IE 6 months after surgery) in patients with IE with or without events. Cytokines IL-1β and IL-6 positively correlated with each other, with leukocytes and NLR. ROC analysis determined that IL-1β and NLR had the most favorable features for the diagnosis of IE [IL-1β AUC 0.816 (p=0.02), NLR AUC 0.807 (p=0.03)]. IL-6 did not show a diagnostic value in IE. The threshold value for IL-1β was 0.00029 (sensitivity 86.4%, specificity 60.0%, prognostic value of negative result 75.0% and positive 76.0%, AUC 0.761; p=0.008). Conclusion. The valve macrophages of patients with IE express elevated levels of proinflammatory cytokines IL-1β and IL-6, regardless of etiological affiliation or complicated course of IE. IL-1β has a high diagnostic value for determining the inflammatory activity in IE.

Inhibition of caspase 1 reduces blood pressure, cytotoxic NK cells, and inflammatory TH17 cells in placental ischemic rats

Preeclampsia (PE) is characterized by maternal hypertension, fetal growth restriction (FGR), and increased inflammation and immune activation, including cytotoxic NK cells (cNKs) and inflammatory T-Helper17 cells (T H 17s). Caspase 1 activity directly leads to release of the inflammatory cytokines IL1β and IL18. Using the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia, we tested the hypothesis that inhibition of caspase 1 with Belnacasan in RUPP rats will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant 10–12-week-old Sprague Dawley rats underwent the RUPP or Sham procedure and received either vehicle or Belnacasan (50mg/kg) daily i.p. from GD14 through GD19: RUPP + vehicle, RUPP + Belnacasan, Sham + vehicle, Sham + Belnacasan. Carotid catheters were placed on GD18. On GD19, MAP was measured, animals were euthanized, and blood and tissues were collected for analysis. Bioplex and flow cytometry analysis were performed on placental tissues. Placental IL1β was markedly increased in RUPP rats vs. Sham rats (44.2 vs. 21.67 pg/mg, p=0.0009). Belnacasan treatment significantly reduced IL1β in RUPP rats (21.90 pg/mg; p=0.0006 vs RUPP). Likewise, placental IL18 was increased in RUPP rats vs Sham (27.1 vs 6.7 pg/mg, p=0.007), and inhibition of caspase 1 reduced RUPP IL18 (6.2, p=0.01 vs RUPP) to Sham levels. No significant differences in IL1β or IL18 were observed in treated Sham rats. These data show the administered Belnacasan dose is effective against Caspase 1 activity. Caspase 1 inhibition reduced placental cNKs in treated-RUPP vs control RUPP (0.155% vs. 0.362 % gated; p=0.043). Belnacasan treatment also reduced placental T H 17s in RUPP rats vs. control RUPPs (1.053% vs 7.25% gated; p=0.003). Increased MAP was observed in RUPP rats vs Sham (131.5 mmHg vs 104.8 mmHg; p<0.0001) and was reduced in RUPP + Belnacasan (117.5 mmHg; p=0.0016 vs RUPP). No changes were observed in MAP of Sham rats treated with Belnacasan. Placental reactive oxygen species (ROS) were elevated in RUPP vs Sham (456.4 vs 198.8 RLU/min/mg, p=0.029). Caspase 1 inhibition significantly reduced ROS in treated RUPP rats (210.3, p=0.031) vs RUPP), and had no effect on ROS in treated Sham rats (156.3). Caspase 1 inhibition had no effect on fetal weight or placental efficiency in any groups. Additional analyses will include assessment of other cytokines in blood and tissue, as well as vascular function in all groups. In conclusion, caspase 1 inhibition reduces placental T H 17 and cNK populations and reduces MAP in RUPP rats. These data suggest that caspase 1 is a key contributor to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes in PE. This work was supported by National Institutes of Health Grants T32HL105324 to C. A. Shields, F31HL165852 to Xi Wang, and R01HL151407 to D. C. Cornelius. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Depression is one of the main mental disorders. Pharmacological treatment of depression is often associated with delayed effects or insufficient efficacy. Consequently, there is a need to discover new therapeutic methods to cope with depression faster and more effectively. Several lines of evidence indicate that the use of probiotic therapy reduces depressive symptoms. Nonetheless, the exact mechanisms linking the gut microbiota and the central nervous system, as well as the potential mechanisms of action for probiotics, are still not entirely clarified. The aim of this review was to systematically summarize the available knowledge according to PRISMA guidelines on the molecular mechanisms linking probiotics and healthy populations with subclinical depression or anxiety symptoms, as well as depressed patients with or without comorbid somatic illnesses. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Twenty records were included. It has been found that probiotic administration is linked to a significant increase in BDNF levels during probiotic treatment compared to the placebo (SMD = 0.37, 95% CI [0.07, 0.68], p = 0.02) when considering the resolution of depressive symptoms in depressed patients with or without comorbid somatic illnesses. CRP levels were significantly lower (SMD = -0.47, 95% CI [0.75, -0.19], p = 0.001), and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], p < 0.0001) in probiotic-treated patients compared to the placebo, however, only among depressed patients with somatic co-morbidities. There were no significant differences in IL-1β, IL-6, IL-10, TNF-α, and cortisol levels after probiotic administration between the intervention and control groups (all p > 0.05). Firm conclusions on the effectiveness of probiotics and their possible association with inflammatory markers in the healthy population (only with subclinical depressive or anxiety symptoms) cannot be drawn. The advent of clinical trials examining the long-term administration of probiotics could evaluate the long-term effectiveness of probiotics in treating depression and preventing its recurrence.

Effect of 6 weeks of aerobic training with nanocurcumin consumption on IL1β, nitric oxide, and depression in women with metabolic syndrome

Backgrounds and ObjectivesThe use of anti-inflammatory supplements is important in improving the executive function of obese people. This research aims to investigate the effect of 6 weeks of aerobic exercise with moderate intensity as well as the consumption of nanocurcumin on IL1β, nitric oxide (NO), and depression in women aged 60–65 with metabolic syndrome.Materials and MethodsFourty-four women with metabolic syndrome were randomly selected and divided into four groups of 10 based on their use of nanocurcumin supplement. The treatment included the training (T), nanocurcumin (N), training + nanocurcumin (TN), and the control groups. The groups exposed to training performed aerobic exercise for 6 weeks (three sessions per week). Blood samples were obtained before and after the training period for antioxidant indicators and lipid degradation measurement. Also, the Beck anxiety questionnaire was used for evaluating levels of anxiety. T-test and one-way analysis of variance (ANOVA) tests were used for the assessment of within-group and between-group differences, respectively.ResultsThere was a significant difference in IL1β, NO, and depression before and after exercise in all three experimental groups (p ≤ 0.05). Also, the results showed a significant difference in the level of NO and depression in the experimental groups. The highest decrease in these variables was observed in the T and TN groups (p ≤ 0.05).ConclusionThese findings indicated that 6-week nanocurcumin supplementation with aerobic training is a suitable method for reducing IL1β, NO, and depression, preventing metabolic, cardiovascular, and inflammatory diseases in women with metabolic syndrome.Name of the registry: IR.SEMUMS.REC.1396.107Trial registration number: IRCT2017082335857N1

Assessing the variability and the role of inflammatory cytokines and monocyte chemoattractant protein-1 (MCP-1) in predicting stroke among hypertensives: A case-control study.

Atherosclerosis is a complex lipid-driven inflammatory disease in which numerous cell types and inflammatory mediators are involved in the progression of hypertension to stroke. Mediators' markers that could predict the progression of hypertension to stroke are of research importance. We assessed the predictive value of individual and combined cytokines and monocyte chemoattractant protein-1 (MCP-1) among hypertensives with or without stroke. In a case-control study, we enrolled 63 cases with stroke and hypertension (HPT-S), 59 stroke-free hypertensives (HPT), and 53 stroke free normotensives as controls (CS). Sociodemographic data and blood samples were collected for the estimation of Interleukin-10 (IL-10), IL-6, IL-8, IL-1β and monocyte chemoattractant protein-1 (MCP-1) using commercially available ELISA kits from Biobase Biotech, Shanghai, China. The Receiver Operator Characteristics (ROC) analysis was used to calculate diagnostic accuracy for cytokines in predicting stroke among hypertensives. A combined bioscore model of IL-10 and MCP-1 was generated to predict stroke among hypertensives. The multiple logistic regression analysis was used to assess the chances of IL-10 and MCP-1 in predicting stroke among hypertensives. Statistical analyses were performed using R-language. The HPT-S group had significantly higher levels of MCP-1 and IL-10 compared to the HPT and CS groups (p < 0.05). There was no significant difference in IL-1β, IL-8 and IL-6 amongst the three study groups. MCP-1 and IL-10 were predictive of stroke occurrence among hypertensives and were used to develop a bioscore model. An elevated MCP-1 and IL-10 with a bioscore 2 had a predictive accuracy of 0.81, a sensitivity of 0.77 and specificity of 0.84. At a bioscore of 1, the sensitivity and specificity for predicting stroke among hypertensives was 97.0% and 61.0% respectively. In a binary logistic regression, having a bioscore of 1 [aOR = 20.43, 95% CI (2.17-192.62), p = 0.008] or 2 [aOR = 26.00, 95% CI (2.92-231.31), p = 0.003] were significantly associated with stroke occurrence among hypertensives. Higher levels of IL-10 with a concomitant level of MCP-1 could serve as a good predictor of stroke among hypertensives. Subsequently, MCP-1 may prove useful as a therapeutic target for atherosclerosis in hypertensives. Combined bioscore of MCP-1 and IL-10 could serve as a good predictor of stroke among hypertensives.

Poster 217: Local and Systemic Comparison of Senescent Profiles in Acute Knee Injury

Poster 217: Local and Systemic Comparison of Senescent Profiles in Acute Knee Injury

Comparison of Rhomboid Intercostal Block, Erector Spinae Plane Block, and Serratus Plane Block on Analgesia for Video-Assisted Thoracic Surgery: A Prospective, Randomized, Controlled Trial.

Background Thoracic surgery is one of the most painful surgical steps. An important tool for managing postoperative pain is effective postoperative analgesia. This research aimed at comparing the analgesic roles of three new fascial block techniques in the postoperative period after video-helped thoracoscopic operation (VATS). Methods We randomly allocated ninety patients into three teams experiencing ultrasound-directed serratus plane block, erector spinae plane block, and the rhomboid intercostal block, respectively. 0.4% ropivacaine of 20 mL was received by all groups. Outcomes. At 0–12 hours, sufentanil consumption was significantly lower in the RIB (35.2 ± 3.3 mg) and ESP (35.4 ± 2.8 mg) groups than that in the SAB (43.3 ± 2.7 mg) group (P < 0.001), and no obvious diversity in sufentanil consumption was shown between the RIB and ESP groups (P=0.813). At 12–24 hours, sufentanil consumption was greatly lower in the RIB and ESP groups than that in the SAB group (P < 0.001), and no great diversity in sufentanil consumption was found between the RIB and ESP groups (P=0.589). No great diversity in sufentanil consumption was shown between the RIB (50.4 ± 1.4 mg), ESP (50.4 ± 1.5 mg), and SAB (51.0 ± 1.7 mg) groups at 24–48 hours (P=0.192). At 6, 12, 18, and 24 hours, the postoperative dynamic NRS scores were significantly lower in the RIB and ESP groups than in the SAB group ((P < 0.05) for all contrasts). Nevertheless, no great diversity was observed in postoperative pain marks at 0.5, 1, 3, 6, 12, 18, 24, 36, and 48 hours after the surgery across the three groups. No statistical diversity was found in the postoperative NRS mark between groups RIB and ESP within 48 hours after surgery in case of active patients ((P < 0.05) for all contrasts). At 24 hours after surgery, a significant difference in IL-1β and IL-6 inflammatory factor concentrations was found between RIB and ESP compared with SAB block ((P < 0.05) for all contrasts). However, no great diversities were observed in IL-1β, and IL-6 inflammatory factor concentrations between RIB, ESP, and SAB at 24 hours preoperatively and at 48 hours postoperatively ((P < 0.05) for all comparisons). Conclusion The dosage of sufentanil can be effectively reduced by ultrasound-directed rhomboid intercostal block and erector spinae plane block within 24 hours after VATS surgery, and pain can be relieved effectively within 24 hours by comparing with serratus plane block.

Comparison of cognitive impairments with lipid profiles and inflammatory biomarkers in unipolar and bipolar depression

Cognitive impairments is one of important accompanied symptom in Unipolar depressive disorder (UD) and bipolar disorder (BD) that was hard to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. In this study, we could highlight the difference of cognitive ability in UD and BD by testing lipid profiles and inflammatory biomarkers in major depressive episodes (MDE). 207 subjects (96 unipolar and 111 bipolar depressed patients) were included in this study. We applied Montreal Cognitive Assessment (MoCA) to test cognitive ability. The 24-item Hamilton Depression Rating Scale was used for assessment at the beginning of treatment. A series of clinical variables and lipid profiles were collected from clinic record. We detected pro-inflammatory biomarkers Interleukin-1β (IL-1β), Interleukin-6 (IL-6), C-reaction protein (CRP) levels and brain-derived neurotrophic factor (BDNF) by enzyme linked immunosorbent assay. From the results, cognitive impairments were more popular in BD than UD, most obviously in severe cognitive impairments (MoCA score<23). And UD showed better cognitive ability than BD in MoCA, particularly in language domain. Compared lipid profiles like total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and lipoprotein α (Lpα), we found that ApoB was higher in BD than UD that maybe a risk factor in cognition. There was no obviously difference in TC, TG, HDL-C, LDL-C, ApoA1, or Lpα. Also, we found CRP level in BD was higher than UD, and showed no significant difference in IL-1β and IL-6 levels. Furthermore, BDNF level which was neurotrophic biomarker for cognition and mood was significantly declined in BD compared with UD. Correlation analysis showed that ApoB and CRP was negative closed associated with MoCA scores. And BDNF level was positive related with cognitive ability in MDE patients. From our results mentioned that quantitative lipid profiles and inflammatory biomarkers analysis might help to objectively identify between these disorders and up our understanding of their pathophysiology. And ApoB, CRP and BDNF could be as potential peripheral candidates in cognitive evaluation to distinguish UD and BD.

Does the high sulfur content in apricots affect oxidative stress?

Apricots are one of the most important fruits that can be produced worldwide. Most of the importer countries are sensitive about sulfur which is used in the protection of dried apricots. The objective of this study was to compare the effects of feeding with high and low sulfur content apricots on oxidative stress parameters of the liver. In total, 42 Wistar albino rats were fed for 12 weeks with the use of dried apricots containing different amounts of sulfur and sun-dried apricots. There was no significant difference in IL-1β, 8-OHdG and TOS levels between the control group and the group fed with sun dried apricots. There was no statistically significant difference between the groups fed with low and high sulfur-containing apricots.Non-necrotic changes were observed in 3000 ppm and 4000ppm groups in microscopic examination. No significant effect of feeding with sulfur treated apricots was found in the liver tissues of rats.

Efficacy of a nanoparticle vaccine administered in-ovo against Salmonella in broilers.

Salmonella is a zoonotic pathogen that persists in poultry. Salmonella vaccines that can be delivered in-ovo can be cost-effective and can decrease Salmonella load in poultry. This study evaluates the efficacy of a Salmonella chitosan-nanoparticle (CNP) vaccine, administered in-ovo, in broilers. CNP vaccine was synthesized with Salmonella Enteritidis (SE) outer-membrane-proteins (OMPs) and flagellin proteins. At embryonic-d18, one-hundred-thirty-six eggs were injected with 200μl PBS or 1000μg CNP into the amniotic cavity. At d1-of-age, 132 chicks were allocated in 6 pens/treatment with 11 chicks/pen. At d7, birds were orally challenged with 1×109 CFU/bird SE. At d1, 8h-post-challenge, d14, and d21, serum anti-SE-OMPs IgY were analyzed. At d14 and d21, cloacal swabs and bile anti-SE-OMPs IgA, CD4+/CD8+-T-cell ratios, and ceca SE loads were analyzed. At d21, cecal tonsil IL-1β, IL-10, and iNOS mRNA were analyzed. Body-weight-gain (BWG) and feed-conversion-ratio (FCR) were recorded weekly. Data were analyzed by Student’s t-test at P<0.05. There were no significant differences in BWG or FCR between vaccinated birds compared to control. At d1, CNP-vaccinated birds had 5.62% greater levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 8h-post-challenge, CNP-vaccinated birds had 6.39% greater levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 2wk-post-challenge, CNP-vaccinated birds had 7.34% lower levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 1wk-post-challenge, CNP-vaccinated birds had 15.30% greater levels (P<0.05) of bile anti-SE-OMPs IgA, compared to control. At d14 and d21, CNP-vaccinated birds had 0.62 and 0.85 Log10 CFU/g, decreased SE ceca load (P<0.05), respectively, compared to control. There were no significant differences in CD4+/CD8+-T-cell ratios between vaccinated birds compared to control. There were no significant differences in IL-1β, IL-10, iNOS mRNA between vaccinated birds compared to control. Findings demonstrate that the in-ovo administration of CNP vaccine can induce an antigen-specific immune response against SE and can decrease SE cecal load in broilers.

Night shift schedule alters endogenous regulation of circulating cytokines

Night shift work is a risk factor for viral infection, suggesting that night shift schedules compromise host defense mechanisms. Prior studies have investigated changes in the temporal profiles of circulating cytokines important for priming and restraining the immune response to infectious challenges from night shift work, but not by way of a 24-h constant routine of continuous wakefulness devoid of behavioral or environmental influences. Hence the true endogenous pattern of cytokines, and the combined effect of sleep loss and circadian misalignment on these cytokines remains unknown. Here, 14 healthy young men and women underwent three days of either a simulated night shift or a simulated day shift schedule under dim light in a controlled in-laboratory environment. This was followed by a 24-h constant routine protocol during which venous blood was collected at 3-h intervals. Those who had been in the night shift schedule showed lower mean circulating TNF-α (t13 = -6.03, p < 0.001), without any significant differences in IL-1β, IL-8 and IL-10, compared with those who had been in the day shift (i.e., control) schedule. Furthermore, circulating IL-6 increased with time awake in both shift work conditions (t13 = 6.03, p < 0.001), such that temporal changes in IL-6 were markedly shifted relative to circadian clock time in the night shift condition. These results indicate that night shift work compromises host defense by creating cytokine conditions that initially impede anti-viral immunity (lower TNF-α) and may eventually promote autoimmunity (mistimed rise in IL-6).

Evaluation of aqueous cytokine levels in eyes with Fuchs endothelial corneal dystrophy and bullous keratopathy

To evaluate cytokine levels in the aqueous humor (AH) of patients with Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). The study included 74 patients (74 eyes). The first group consisted of 31 patients (72.7±9.2 years) with FECD; the second group included 35 patients (72.4±9.1 years) with BK. The control group comprised 8 patients (74.3±4.1 years) with immature cataract. Before surgery, patients underwent pachymetry of the central cornea (RTvue-100 OCT, Optovue, USA). Patients of groups 1 and 2 underwent endothelial keratoplasty (DSAEK or DMEK), or penetrating corneal transplantation. Patients of the control group underwent phacoemulsification with implantation of intraocular lens. The initial stage of the surgery involved AH sample collection for evaluation of cytokine levels (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, G-CSF, GM-CSF, IFNγ, MCP-1, MIP-1β and TNF-α) by fluorescent flow cytometry using the Bio-Plex Pro Human Cytokine Panel, 17-plex (Bio-Rad, USA). Multiplex analysis of the AH content did not show any statistically significant differences in cytokine levels between decompensated FECD and BK eyes. The levels of IL-6, IL-8, GM-CSF, IFNγ, MCP-1, MIP-1β were significantly elevated in FECD and BK eyes compared with healthy control. An insignificant deviation of IL-4 and IL-13 levels was detected in FECD and BK eyes compared with healthy controls. There were no significant differences in IL-1β and TNF-α (indicators of acute inflammation) between the study groups. The obtained data confirm that FECD and BK are associated with disruption of ocular immune privilege that leads to chronic local inflammation, which in turn causes remodeling of the corneal tissues resulting in fibrosis.

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

BackgroundJoint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model.MethodsThe knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction.ResultsThe number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression.ConclusionsThe results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.

Evaluation of the clinical and biochemical efficacy of erbium, chromium:ytrium-scandium-gallium-garnet (ER,CR:YSGG) laser treatment in periodontitis.

The objective of this study was to evaluate the clinical and biochemical efficacy of erbium, chromium:ytrium-scandium-gallium-garnet (Er,Cr:YSGG) laser treatment, in addition to non-surgical periodontal treatment (NSPT), in periodontitis patients. This was a single-centre, split-mouth, randomized, controlled 6-month clinical trial. Twenty-seven patients with moderate to advanced periodontitis were included in the study. The patients were randomly assigned to a debridement and laser treatment group or control group (debridement alone). Clinical measurements were performed at baseline and 1, 3 and 6months post-treatment. The following parameters were measured: plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), bleeding on probing (BoP), gingival crevicular fluid (GCF) volume and IL-1β and MMP-8 levels in GCF. There were statistically significant clinical improvements in both groups, with no significant between-group differences in PD, CAL, PI and BoP clinical measurements (p < 0.05). As compared with the control group, the GI 1 and 3months post-treatment and BoP 1month post-treatment were significantly improved in the laser group (p < 0.05). There was also a significant reduction in IL-1 β levels in both groups at baseline versus those 1, 3 and 6months later (p < 0.05) There was no statistically significant difference in IL-1β and MMP-8 levels between groups (p < 0.05). Both the treatment modalities resulted in significant improvements in clinical parameters. Within the limitations of this study, Er,Cr:YSGG laser treatment applied in addition to NSPT is indicated to reduce clinical inflammation.

Postoperative Serum Levels of Interleukin-1β (IL-1β), Interleukin-17 (IL-17), and Tumor Necrosis Factor-α (TNF-α) in Patients Following Hip Replacement Surgery for Traumatic Fractured Femoral Neck: A Retrospective Study.

BackgroundThis study aimed to investigate the clinical significance of postoperative serum levels of interleukin-1β (IL-1β), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) in patients who required hip replacement surgery for traumatic fractured neck of femur.Material/MethodsA retrospective study included 180 patients who had hip replacement surgery for traumatic fractured neck of femur and a control group of 100 patients. Differences between the two groups were compared for serum levels of IL-1β, IL-17, and TNF-α, and the Harris Hip Score (HHS) (maximum 100 points) using Pearson’s correlation.ResultsSerum levels of IL-1β, IL-17, and TNF-α in the control group were significantly lower than those in the study group (P<0.05). According to the HHS, there were 53 patients in the excellent group, 65 patients in the good group, 43 patients in the fair group and 19 patients in the poor group. Postoperative indicator analysis showed significant differences in IL-1β, IL-17, and TNF-α levels between the four groups (P<0.05). Clinical indicators increased from the excellent group to the poor group, with significant differences between the four groups (P<0.05). Postoperative levels of IL-1β, IL-17, and TNF-α were significantly decreased (P<0.05). Pearson’s correlation analysis showed a significant correlation with the clinical indicators (P<0.05).ConclusionsIn patients with hip replacement surgery for traumatic fractured neck of femur, measurement of postoperative serum levels of IL-1β, IL-17, and TNF-α were shown to be potential prognostic indicators.

Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis.

The purpose of this study was to test for the role of the P2X7 receptor in localized aggressive periodontitis (LAP). Peripheral blood was obtained from 95 subjects with LAP and 76 healthy unrelated controls (HUCs). Three P2RX7 single-nucleotide polymorphisms (rs1718119, rs2230911, and rs3751143) were genotyped from these subjects, and their peripheral blood samples were stimulated with lipopolysaccharide (LPS) from Escherichia coli and tested for inflammatory markers. The 3 P2RX7 single-nucleotide polymorphisms were in found to be in perfect linkage disequilibrium, and a total of 4 haplotypes and 9 diplotypes were identified among all subjects. For both subject populations, the 9 diplotypes were grouped into 4 functional groups and tested for association with subject inflammatory response. To specifically study the effects of extrinsic activation of the P2X7 receptor in LAP, peripheral blood samples from were stimulated under 3 treatments: LPS, LPS + ATP, and LPS +ATP+ P2X7 selective inhibitor. The effects of these treatments on P2X7 receptor activity were measured through Luminex protein assay. Last, to test whether receptor stimulation was related to P2RX7 expression, relative mRNA levels of P2RX7 were quantified with real-time quantitative polymerase chain reaction. Several associations between the P2RX7 diplotypes and LPS-stimulated blood chemokine/cytokine levels were found between the LAP and HUC populations (P < 0.05). P2X7 activation resulted in statistically significant differences in IL-1β and IL-12p40 concentrations for both subject populations. The relative P2RX7 mRNA levels increased significantly after addition of its inhibitor for both LAP and HUC populations. This study detected an association between P2RX7 functional diplotypes and in vitro immune response of whole blood from subjects with LAP. In addition, we found that inhibition of the activated P2X7 receptor leads to increased P2RX7 mRNA levels, suggesting a feedback loop ( ClinicalTrials.gov NCT01330719). The results of this study suggest that P2RX7 functional diplotypes are associated with LAP and their in vitro immune response to bacteria. Ongoing studies to uncover the mechanistic link between P2RX7 and LAP phenotypes could lead to the development of preventive approaches for susceptible subjects.

The effects of intraperitoneal metoprolol administration on healing of bone defects in rat tibia: a pilot study.

Metoprolol is a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties, devoid of intrinsic sympathomimetic activity. Various studies have suggested the effect of beta-blockers on bone remodeling. We aimed to investigate whether metoprolol affects bone remodeling by altering anti-inflammatory and pro-inflammatory cytokines. Surgical defects of 3mm diameter were created in tibiae of 72 Sprague-Dawley rats. Rats were randomly assigned to a control group without metoprolol treatment (n = 36), and a test group treated with 0.1mg/kg/day metoprolol (n = 36). Six rats from each group were sacrificed at days 0, 1, 3, 5, 7, and 14. The percentages of cells, which showed positive immunohistochemical staining for IL-1β, IL-6, IL-10, and RANKL, were assessed in the defect area. Differences in percentages of stained cells within each of the test and control groups over various time intervals were tested using one-way ANOVA test. A P value of < 0.05 was considered statistically significant. No significant differences in IL-1β, IL-10, IL-6, and RANKL expressions were found between test and control groups at the same interval. Significant reduction was observed at different time intervals in the same group (P < 0.05). Metoprolol did not reduce bone-active cytokine: IL-1β, IL-6, and RANKL. It also did not elevate IL-10 expression levels. Thus, it does not appear to decrease osteoclastogenesis. Results from this animal model help us understand any effect of metoprolol on bone healing by potential contribution to different real-world clinical research.