Levels Of Inflammatory Cytokines In Patients Research Articles

THE INFLUENCE OF THE APOEε4 ALLELE ON PRO-INFLAMMATORY CYTOKINE LEVELS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH ALZHEIMER’S DISEASE

Single nucleotide polymorphisms (SNPs) rs429358 and rs7412, the most commonly investigated variants in the apolipoprotein E gene (APOE) are crucial for APOEε4 carrier status determination. However, their association with inflammatory cytokine levels in patients with dementia due to Alzheimer’s disease (AD) remains unclear. This study aimed to investigate the influence of the APOEε4 allele on pro-inflammatory cytokine levels in the cerebrospinal fluid of patients with AD dementia. The research was conducted on 36 patients with probable dementia due to AD. APOE rs429358 and rs7412 were analyzed using the Real-Time PCR method with allele-specific TaqMan assays, followed by the analysis of APOEε4 allele carrier status. Patients carrying at least one APOEε4 allele were assigned as APOEε4+. Core biomarkers (Aβ42/40 ratio, t-Tau, p-Tau levels), as well as pro-inflammatory cytokine (Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b)) levels, were determined in the patient’s cerebrospinal fluid (CSF) using Enzyme-linked Immunosorbent Assay (ELISA). Seventeen patients (47.22%) were assigned as APOEε4+. CSF TNF-α levels were significantly higher in APOEε4+ AD dementia patients in comparison to APOEε4- patients (p<0.001), while no significant differences in IL-1b levels between these two groups were obtained. Correlation analysis showed that TNF-α negatively correlated with the Aβ42/40 ratio (p=0.033), while positive correlation with t-Tau and p-Tau was observed (p=0.001, p=0.015, respectively). These findings highlight the potential significance of TNF-α in the context of APOEε4 positivity and its implications in AD pathology.

Monoclonal antibody precision therapy targeting inflammation for bipolar disorder: a narrative review.

Bipolar disorder (BD) is a severe mental disorder with various hypotheses regarding its pathogenesis. This article provides a summary of numerous studies on the variations in inflammatory cytokine levels in patients with BD and the effects of treatment with antipsychotics, mood stabilizers, and antidepressants on these levels. In addition, patients with autoimmune diseases who use anti-inflammatory monoclonal antibodies experience symptoms, such as depression, anxiety, and insomnia. These pieces of evidence suggest a potential association between immune inflammation and BD and offer new possibilities for therapy. Building upon this relationship, the authors propose an innovative approach for treating BD through individualized and precise therapy using anti-inflammatory monoclonal antibody drugs. To support this proposal, the authors compile information on pharmacological effects and relevant studies, including trials of various anti-inflammatory therapeutic monoclonal antibody drugs (e.g. infliximab, tocilizumab, and canakinumab) for the potential treatment of BD and its associated side effects in psychiatry. The authors categorize these anti-inflammatory monoclonal antibody drugs into levels I-IV through a comprehensive analysis of their advantages and disadvantages. Their potential is examined, and the need for further exploration of their pharmaceutical effects is established.

Effects of externally-applied, non-pharmacological Interventions on short- and long-term symptoms and inflammatory cytokine levels in patients with knee osteoarthritis: a systematic review and network meta-analysis.

With the continuous development of clinical medicine, an increasing number of non-pharmacological interventions have been applied for the treatment of knee osteoarthritis (KOA), with the results of several recent randomized controlled trials (RCTs) showing that a variety of externally-applied, non-pharmacological interventions (EANPI) can improve symptoms and inflammation in patients with KOA. However, the relative benefits and disadvantages of non-drug therapies remain uncertain, and an optimal treatment strategy has not yet been determined. This study applied network meta-analysis (NMA) to compare and rank the effectiveness of EANPI on the short- and long-term clinical symptoms and inflammatory cytokine levels in patients with KOA. Two independent researchers searched online databases and performed manual retrieval of related citations to identify RCTs that met the selection criteria for the network meta-analysis. These researchers retrieved studies indexed from database inception to August 2023 and performed data extraction and assessment of the risk of bias. The analysis included 80 RCTs involving 8440 participants and nine externally-applied, non-pharmacological therapies, namely extracorporeal shock wave, radiofrequency, acupotomy, laser therapy, Tuina therapy, kinesio taping, electroacupuncture, platelet-rich plasma injection, and ozone therapy. The treatment courses ranged from 1 to 12 weeks, with follow-up periods ranging from 4 to 24 weeks. The results of the NMA indicated that each non-drug therapy was superior to sham intervention in improving all outcome indicators. Except for the visual analog scale (VAS) and Western Ontario MacMaster (WOMAC) pain outcomes, all non-drug therapies had better efficacy than pharmacological treatments. For short-term VAS and tumor necrosis factor-alpha (TNF-α), extracorporeal shock wave performed better than other therapies (90.2% and 85.2% respectively). Radiofrequency therapy may be the most promising method to reduce long-term VAS, short- and long-term WOMAC pain, and interleukin (IL)-1β level (84.8%, 97.8%, 90.1%, 94.8% respectively). Tuina therapy may be a significant choice for short- and long-term outcomes of WOMAC function and range of motion (ROM). The results of the comprehensive comparison of the outcome indicators in 9 different EANPI indicated that radiofrequency and Tuina therapy were more effective and consistently ranked high in improving clinical symptoms in the short and long term. Radiofrequency is effective at relieving pain, and Tuina therapy can be given priority for treatment when hypofunction is the main symptom. EANPI to improve pain symptoms may be related to the regulation of inflammatory cytokine levels, which may be a potential mechanism of action. https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42023464177.

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: A post-hoc study of the CONFIDENCE trial

BackgroundAdipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). MethodsFour hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. ResultsIn total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1β and IFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in leptin or FGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight, waist and HbA1c, the between-group differences were found in ΔIL-1β (exenatide vs. insulin: P = 0.048; and exenatide vs. pioglitazone: P = 0.003, respectively) and ΔIFN-γ (exenatide vs. insulin: P = 0.049; and exenatide vs. pioglitazone: P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔIL-1β (β = 0.753; 95 % CI, 0.137–1.369; P = 0.017). After adjusting for treatment effects, Δweight was also be correlated with ΔFGF21 (β = 1.097; 95%CI, 0.250–1.944; P = 0.012); furthermore, ΔHOMA-IR was correlated with Δleptin (β = 0.078; 95%CI, 0.008–0.147; P = 0.029) as well. However, ΔHOMA-IR was not significantly associated with ΔIL-1β after adjusting for treatment effects (P = 0.513). ConclusionExenatide treatment led to significant changes of inflammatory cytokines levels (IL-1β and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.

Inflammatory Cytokines Changed in Patients With Depression Before and After Repetitive Transcranial Magnetic Stimulation Treatment.

Studies have found that repetitive transcranial magnetic stimulation rTMS can produce antidepressant effects by affecting inflammatory cytokines in patients with depression, which plays a key role in the therapeutic mechanism of antidepressants. This study aimed to explore the changes in inflammatory cytokine levels in patients with depression after 4 weeks of rTMS treatment to determine the possible antidepressant mechanism of rTMS. This prospective, double-blind, pseudo-stimulus-controlled study was conducted, and a total of 57 patients with depression and 30 healthy controls were recruited. Patients were randomly divided into the active rTMS (n = 29) and sham rTMS groups (n = 28). The Hamilton Depression Scale was used to evaluate depressive symptoms and their severity. The serum levels of seven inflammatory cytokines were measured using enzyme-linked immunosorbent assay. Inflammatory cytokines include high-sensitivity C-reactive protein (CRP-hc); tumor necrosis factor (TNF-α); interferon (IFN-γ); interleukin-2 (IL-2); interleukin-4 (IL-4); interleukin-6 (IL-6); and interleukin-8 (IL-8). At baseline, TNF-α (F = 36.699, p < 0.001), IFN-γ (F = 8.907, p < 0.001), IL-4 (F = 66.256, p < 0.001), and IL-2 (F = 9.162, p < 0.001) levels in the depression group were significantly different from those of healthy controls. In the self-control analysis of the active rTMS group, the levels of IL-2 and CRP-hc increased significantly after 2 and 12 weeks of treatment. In the sham-rTMS group, IFN-γ increased after 2 and 12 weeks of treatment. Our results revealed that the changes in inflammatory cytokines after rTMS treatment showed different patterns compared to the sham group, suggesting that the antidepressant effect of rTMS may be related to changes in inflammatory cytokines.

Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis

Background & AimsPsychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators.MethodsThe perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded.ResultsSeventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks.ConclusionsMBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH.Clinical Trials registrationThis study is registered at ClinicalTrials.gov (NCT02950077).Lay summaryAutoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

Inflammatory Cytokine Levels in Patients with Sporadic Amyotrophic Lateral Sclerosis

Objectives: In the present study, inflammatory factors, including interleukin (IL) and tumor necrosis factor-α (TNF-α) in the peripheral blood of patients with sporadic amyotrophic lateral sclerosis (sALS), were evaluated, and the issue of whether these variables were associated with the progression and severity of the disease examined. Methods: Data on inflammatory factors, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, were retrospectively collected from 248 sALS patients admitted to the Chinese PLA General Hospital between March 2018 and March 2021. The relationships between the variables and clinical features, including gender, age at onset, site of onset, time from onset to hospital admission, ALS functional rating scale score, and diagnostic category were analyzed. Results: IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α levels were elevated in 43.75%, 7.04%, 16.42%, 25.35%, 1.41%, and 50.72% of ALS patients, respectively, compared with the normal value range. IL-2 and IL-6 levels were inversely associated with the ALS functional rating scale score (r = −0.280, p = 0.004 and r = −0.198, p = 0.048). Conclusion: Elevated levels of inflammatory cytokines support the hypothesis of an inflammatory response in ALS, and IL-2 and IL-6 may be used as an inflammation-related biomarker for disease severity.

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

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

Improvement of clinical outcome, laboratory findings and inflammatory cytokines levels using plasmapheresis therapy in severe COVID-19 cases

IntroductionCytokine storm is one of the consequences of the severe forms of COVID-19 due to excessive immune response. In this study, we investigated the therapeutic effect of plasmapheresis and its role on the inflammatory cytokines levels in patients suffering from severe COVID-19. MethodsIn plasmapheresis group, 22 severe cases of COVID-19 receiving three cycles of plasmapheresis with time interval of 24–36 h and 22 COVID-19 patients as the control group were enrolled. Clinical history and laboratory parameters as well as IL-1, IL-6, IFN-γ and IL-17 cytokines serum levels in the time points of before and after plasmapheresis were studied. ResultsIn severe COVID-19 patients, plasmapheresis significantly improved clinical and laboratory parameters such as cough, weakness, fever, blood oxygen saturation and CRP levels. Serum levels of IL-1, IL-6, IFN-γ and IL-17 in the group of patients receiving plasmapheresis, had a significant decrease following plasmapheresis courses. Although only IL-6 level in the control group had a significant decrease between the days 1–14 of disease. Also, at both time points of before and after plasmapheresis, serum levels of IL-1, IL-6, IFN-γ and IL-17 were inversely correlated to blood oxygen saturation. ConclusionBased on the obtained results, plasmapheresis therapy in severe forms of COVID-19 can effectively improve the clinical symptoms of the disease and reduce inflammatory markers. Therefore, it is suggested that plasmapheresis can be evaluated in standard treatment protocols for severe forms of COVID-19.

COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction.

Vascular injury has emerged as a complication contributing to morbidity in coronavirus disease 2019 (COVID-19). The glycosaminoglycan hyaluronan (HA) is a major component of the glycocalyx, a protective layer of glycoconjugates that lines the vascular lumen and regulates key endothelial cell functions. During critical illness, as in the case of sepsis, enzymes degrade the glycocalyx, releasing fragments with pathologic activities into circulation and thereby exacerbating disease. Here, we analyzed levels of circulating glycosaminoglycans in 46 patients with COVID-19 ranging from moderate to severe clinical severity and measured activities of corresponding degradative enzymes. This report provides evidence that the glycocalyx becomes significantly damaged in patients with COVID-19 and corresponds with severity of disease. Circulating HA fragments and hyaluronidase, 2 signatures of glycocalyx injury, strongly associate with sequential organ failure assessment scores and with increased inflammatory cytokine levels in patients with COVID-19. Pulmonary microvascular endothelial cells exposed to COVID-19 milieu show dysregulated HA biosynthesis and degradation, leading to production of pathological HA fragments that are released into circulation. Finally, we show that HA fragments present at high levels in COVID-19 patient plasma can directly induce endothelial barrier dysfunction in a ROCK- and CD44-dependent manner, indicating a role for HA in the vascular pathology of COVID-19.

Effects of Probiotic Preparations on Inflammatory Cytokines in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

To summarize and assess the effects of probiotic preparations on inflammatory cytokine levels in patients with Chronic Kidney Disease (CKD). We searched through the PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Wan Fang databases for Randomized Controlled Trials (RCTs) that report the impact of probiotic preparations on inflammatory cytokines in CKD patients. Outcomes were composed of serum levels of CReactive Protein (CRP), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), serum urea, creatinine, uric acid, Para-Cresol Sulfate (PCS), and Indoxyl-Sulfate (IS). The Mean Differences (MDs) with 95% Confidence Intervals (CIs) were considered as effect estimates. Sensitivity analysis and Egger's linear regression test were performed to evaluate the stability of results and publication bias. This study was registered with PROSPERO number CRD42020176557. Sixteen studies met the inclusion criteria. Evidence showed that serum CRP levels were decreased in the intervention group (WMD, -12.29, 95% CI, -16.41 to -8.16, p = 0). The IL-6 was significantly reduced only in the prebiotic group (SMD, -0.73, 95% CI, -1.3 to -0.16, p = 0.012). However, no reduction was observed in TNF-α (SMD, -0.07, 95% CI, -0.51 to 0.38, p = 0.772). Moreover, there was no significant change in serum uremic toxin, including creatine, urea, uric acid, PCS, and IS. Probiotic preparations decrease the serum levels of inflammatory cytokines in CKD patients but do not affect the serum uremic toxin levels. The results of this meta-analysis suggest essential guidance for treatment decisions in clinical practice.

CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway.

Cerebral ischemia-reperfusion (I/R) injury is an inflammation-related disease. CHRFAM7A can regulate inflammatory responses. Therefore, the present study investigated the mechanism of CHRFAM7A in cerebral I/R injury. CHRFAM7A expression and inflammatory cytokine levels in patients with cerebral I/R injury and oxygen-glucose deprivation/reperfusion (OGD/R)-treated microglia were detected. The proliferation, inflammatory cytokine expressions, nod-like receptor protein 3 (NLRP3) level, cell pyroptosis, and viability and lactate dehydrogenase (LDH) activity in OGD/R-treated microglia were detected after CHRFAM7A overexpression. The NLRP3/Caspase-1 pathway was activated to assess the effect of CHRFAM7A on microglia. Expressions of microglial M1 phenotype marker iNOS and M2 marker Arg1 were detected. Downregulated CHRFAM7A and elevated inflammatory cytokine levels were observed in patients with cerebral I/R injury and OGD/R-treated microglia. In OGD/R-treated microglia, CHRFAM7A overexpression promoted cell proliferation and viability, reduced inflammation and LDH activity, and inhibited NLRP3 inflammasome activation and cell pyroptosis. Mechanically, CHRFAM7A inhibited microglia pyroptosis via inhibiting the NLRP3/Caspase-1 pathway and reduced cell inflammatory injury via promoting microglia polarization from M1 to M2. Overall, CHRFAM7A overexpression attenuated cerebral I/R injury by inhibiting microglia pyroptosis in a NLRP3/Caspase-1 pathway-dependent manner and promoting microglia polarization to M2 phenotype.

Effect of Acupuncture Combined with Tuina on Cervical Curvature and Serum Inflammatory Cytokine Levels in Patients with Cervical Spondylosis

To study the effects of acupuncture and tuina by stages on cervical curvature, serum interleukin-4, interleukin-8 and tumor necrosis factor-alpha in patients with cervical spondylosis. A total of 94 patients with cervical spondylosis admitted from June 2020 to June 2021 were divided into the control group and the study group through random number table with 47 cases in each group. Patients in the control group were treated with tuina and patients in the study group were treated with acupuncture and tuina by stages. One course of treatment was 21 d and both groups were treated for 2 courses. The clinical effects of the patients in the two groups after treatment were compared, the cervical spine curvature and visual analogue scale scores of patients in the two groups before and after treatment were compared and the serum levels of interleukin-4, interleukin-8 and tumor necrosis factor-alpha before and after treatment were compared. The total clinical effective rate of patients in the study group was 91.48 % (43/47), which was higher than 68.09 % (32/47) of patients in the control group. After treatment, the C value of cervical spine physiological curvature of patients in the two groups was higher than that before treatment and the visual analog scale scores, serum interleukin-4, interleukin-8, tumor necrosis factor-alpha levels decreased. The improvement of patients in the study group was better than that in the control group (all p<0.05). Acupuncture and tuina to treat patients with cervical spondylosis by stages can better improve the curvature of the patient’s cervical spines, reduce pain, inhibit inflammation in the body and improve the therapeutic effect.

Low Vitamin D Levels can Effect the Balance of Immun Mediators in Fibromyalgia Syndrome Objective

Objective: To investigate the relationship between vitamin D levels and inflammatory cytokine levels in patients with Fibromyalgia Syndrome (FMS). Materials and Methods: 29 women with FMS who were diagnosed according to American College of Rheumatology (ACR) 2010 fibromyalgia diagnostic criteria and 25 healthy women as the control group was included in the study. Serum levels of vitamin D, Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP), and inflammatory cytokines (IL-2, IL-4, IL-6, IL-12, IFN-γ) were analyzed using by ELISA method. Widespread body pain, fatigue, morning stiffness, cognitive symptoms, somatic symptoms, Fibromyalgia Impact Questionnaire (FIQ) scores were evaluated in patients with FMS. Results: Vitamin D, VDR, and VDBP levels were found to be higher in the healthy individuals compared to the patients with FMS (p<0.001, p<0.002, p<0.001, respectively). Correspondingly, pro-inflammatory (IL-2, IL-12, IFN-γ), anti-inflammatory (IL-4), and both pro and anti-inflammatory (IL-6) cytokine levels of the control group were higher than the patients with FMS (p<0.001, p<0.006, p<0.004, p<0.001, p<0.049, respectively). Conclusion: Low vitamin D levels in FMS may negatively affect the release of inflammatory cytokines and this functional relationship may be in the etiology of this chronic pain disorder

Analysis of the changes of inflammatory cytokine levels in patients with critical coronavirus disease 2019 undergoing invasive mechanical ventilation

To investigate the relationship between the changes of inflammatory cytokine levels and prognosis of patients with critical coronavirus disease 2019 (COVID-19) undergoing invasive mechanical ventilation (IMV). A retrospective study was conducted. The clinical date of critical COVID-19 patients undergoing IMV who were hospitalized in Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 4th to March 25th in 2020 were collected. At the same time, the inflammatory cytokine levels including interleukins (IL-2, IL-4, IL-6, IL-10) and tumor necrosis factor-α (TNF-α) at 48 hours before IMV and 48 hours after IMV of all the patients, as well as the 48 hours after weaning or right before death were recorded. Multivariate unconditional Logistic regression analysis was used to screen the independent risk factors of death during hospitalization. Among the 43 patients, 13 patients improved and 30 died. Compared with the survival group, the patients in the non-survival group were older (years old: 67.6±7.3 vs. 58.5±11.9, P < 0.05), with higher rates of hypertension, diabetes and coronary heart disease (53.3% vs. 15.4%, 63.3% vs. 23.1%, 26.7% vs. 0%, all P < 0.05), and the time from onset to admission to hospital, admission to ICU and IMV were longer (days: it was 9.17±5.00 vs. 5.07±2.49, 17.10±7.11 vs. 12.23±5.05, and 17.90±7.46 vs. 12.61±5.60, respectively, all P < 0.05). The IL-6 and TNF-α levels on 48 hours after IMV in the non-survival patients increased significantly as compared with those before 48 hours and the surviving patients. Especially, the IL-6 levels increased significantly as compared with those at 48 hours after IMV and 48 hours after weaning in the surviving patients [ng/L: 800.00 (194.25, 2 000.00) vs. 22.03 (6.66, 28.21), 3 204.00 (1 264.88, 5 000.00) vs. 5.00 (3.98, 12.27), both P < 0.01]. The IL-10 level before death in the non-survival patients increased significantly as compared with that at 48 hours after weaning in the surviving patients [ng/L: 55.89 (26.07, 100.14) vs. 3.53 (2.76, 12.36), P < 0.05]. There were no significant differences in the levels of IL-2 and IL-4 between the two groups at every time point. The variables of age, basic diseases, the IL-6 level after IMV were included in the multivariate unconditional Logistic regression analysis, which showed that age [odds ratio (OR) = 0.821, 95% confidence interval (95%CI) was 0.695-0.968], hypertension (OR = 0.027, 95%CI was 0.002-0.378), diabetes mellitus (OR = 0.054, 95%CI was 0.005-0.611), coronary heart disease (OR = 0.042, 95%CI was 0.002-0.968) and the IL-6 level after IMV (OR = 0.902, 95%CI was 0.819-0.994) were independent risk factors for death during hospitalization in patients with critical COVID-19 undergoing IMV (all P < 0.05). The levels of inflammatory cytokine including IL-6, IL-10, and TNF-α increased significantly with aggravation in critical COVID-19 patients undergoing IMV, especially IL-6. IL-6 was an independent risk factor for death of critical COVID-19 patients undergoing IMV.

Aberrations in peripheral inflammatory cytokine levels in substance use disorders: a meta-analysis of 74 studies.

To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs). Systematic review and meta-analysis. Clinical studies that evaluated peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls PARTICIPANTS: SUD patients and healthy controls. PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta-analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random-effects model by the Comprehensive Meta-Analysis version 2 software. Concentrations of interleukin (IL)-6) in 32 studies, tumor necrosis factor (TNF)-α in 28 studies, IL-10 in 20 studies, IL-8 in 17 studies, C-reactive protein in 14 studies, IL-4 in 10 studies, IL-12 in seven studies, monocyte chemoattractant protein (MCP)-1 in 6 studies, TNF-receptor 2 (TNF-R2) in four studies and granulocyte-macrophage colony-stimulating factor (GM-CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon-γ, IL-1β, IL-2, IL-1 receptor antagonist (IL-1RA), transforming growth factor (TGF)-β1, G-CSF, C-C motif chemokine 11, TGF-α and SUDs. People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, C-reactive protein, MCP-1, TNF-R2 and GM-CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.

Change of Serum Inflammatory Cytokines Levels in Patients With Chronic Obstructive Pulmonary Disease, Pneumonia and Lung Cancer.

Objective:This study aimed to investigate the serum inflammatory cytokines levels in patients with COPD, pneumonia and lung cancer, and assess the correlation between the levels of inflammatory cytokines levels and development of these diseases.Methods:Two hundred thirty-two patients including 114 patients with pneumonia, 76 patients with chronic obstructive pulmonary disease (COPD) and 42 patients with lung cancer, and 62 age-matched healthy volunteers as controls were enrolled. The pro-inflammatory cytokine IL-6, IL-2, IFN-γ, TNF-α, anti-inflammatory cytokines IL-4 and IL-10 in serum were analyzed by flow cytometry microsphere array (CBA).Results:We found that the levels of TNF-α and IL-10 in patients with lung cancer, COPD and pneumonia were significantly higher than control group. The IL-6 in the lung cancer group were significantly increased compared with the controls and COPD group, pneumonia group. IFN-γ and IL-2 levels were lower in lung cancer compared with controls and COPD group, pneumonia group. TNF-α, IL-4 and IL-10 levels were increased in patients with COPD and pneumonia compared with controls. In addition, the concentrations of IFN-γ and IL-6 were increased in acute exacerbation COPD (AECOPD) group compared with stable COPD group.Conclusion:In conclusion, elevated TNF-α and IL-10 levels in serum may be related with lung diseases including lung cancer, COPD and pneumonia. Additionally, IFN-γ and IL-6 might be potential biomarkers for the further deterioration of lung disease patients. The increased concentrations of IFN-γ and IL-6 might be used to predict the exacerbation of COPD.

Long non-coding RNA zinc finger antisense 1 expression associates with increased disease risk, elevated disease severity and higher inflammatory cytokines levels in patients with lumbar disc degeneration.

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646–0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1β (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.

Research on the correlation of changes in plasma lncRNA MEG3 with change in inflammatory factors and prognosis in patients with traumatic brain injury.

To study the correlation between the plasma long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) and the levels of inflammatory cytokines in patients with traumatic brain injury (TBI) and to evaluate its prognosis to screen new biological targets for the diagnosis and treatment of TBI. 40 patients with TBI (TBI group) and 40 healthy people (control group) were collected and venous blood was drawn. The plasma MEG3 in subjects was quantitatively analyzed via quantitative Polymerase Chain Reaction (qPCR). Moreover, the levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-8] in plasma in each group were detected via enzyme-linked immunosorbent assay (ELISA). Finally, the correlation analysis was performed for the MEG3 expression level and inflammatory cytokine levels in patients with TBI. Patients were divided into high-expression MEG3 group and low-expression MEG3 group, high-level inflammatory cytokine group and low-level inflammatory cytokine group according to the median, followed by prognosis evaluation. The MEG3 expression level in TBI group was significantly decreased compared to that in control group, and the levels of inflammatory cytokines in plasma, including TNF-α, IL-1β, IL-6, and IL-8, were significantly higher than in control group. The results of the correlation analysis showed that the expression level of plasma MEG3 had a significantly negative correlation with the level of each inflammatory cytokine. The prognostic analysis revealed that the prognosis of patients with high MEG3 expression level and low inflammatory cytokine levels was good, while it was poor in patients with low MEG3 expression level and high inflammatory cytokine levels; the difference was significant. In patients with TBI, the expression level of plasma MEG3 is decreased, while the inflammatory cytokine levels are increased, and there is a significantly negative correlation between the two items. The prognosis of patients with high MEG3 expression level and low inflammatory cytokine levels is good so MEG3 and inflammatory cytokines can be used as biomarkers for diagnosis and treatment of TBI, improving the prognosis of patients.

Effect of Low-Level Laser Therapy in Treatment of Chemotherapy Induced Oral Mucositis

Introduction: Oral mucositis (OM) is an unavoidable condition of the oral cavity that accompanies chemotherapy for various malignant cases. Chemotherapy-induced oral Mucositis (COM) is a frequent complication due to mucotoxic drugs and is known to deteriorate the general health significantly, while negatively affecting the quality of life (QOL). Studies have reported that low-level laser therapy (LLLT) promotes the tissue healing. The objective of the present study was to explore the efficacy of gallium-arsenide (GaAs) laser in treating COM and its impact on inflammatory cytokine levels in patients receiving chemotherapy for various malignancies. Methods: A total of 80 patients with COM received LLLT 6 days/week. OM was graded according to the World Health Organization (WHO) grading scale. The outcome parameters were the serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) measured before, during and after administration of LLLT. Results: After LLLT, a significant decrease was found in the mean values of mucositis grade from 2.35 ± 0.695 to 1.13 ± 0.333 after (P < 0.001). A significant reduction in the level of TNF-α was found after LLLT among breast cancer patients (P = 0.0045), but not in head and neck cancer and lymphoma patients. A significant reduction was also found in IL-6 level after treatment among head and neck and breast cancer patients (P = 0.0307 and 0.019, respectively). Conclusion: The use of GaAs LLLT in treating COM in patients with various malignancies is well tolerated by patients, it results in improvement of mucositis, however; mechanism of action does not seem to be completely linked to the change of pro or anti-inflammatory cytokines.