Serum Levels Of TNF Research Articles

Effectiveness of Borage plus syrup on COVID-19 patients in intensive care units.

COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020-December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-β and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis.

Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is essential for the formation of fully functional multinucleated osteoclasts. DC-STAMP deficient mice, under physiological conditions, exhibit osteopetrosis and develop systemic autoimmunity with age. However, the function of DC-STAMP in inflammation is currently unknown. We examined whether genetic ablation of DC-STAMP attenuates synovitis and bone erosion in TNF transgenic (Tg) and K/BxN serum-induced murine rheumatoid arthritis. We evaluated arthritis onset in Tg(hTNF) mice lacking DC-STAMP and 50:50 chimeric mice by visual examination, measurement of ankle width, micro-CT-scan analysis and quantitation of the area occupied by osteoclasts in bone sections. To further investigate the cellular and molecular events modulated by DC-STAMP, we measured serum cytokines, determined changes in cytokine mRNA expression by monocytes activated with IL4 or LPS/IFNγ and enumerated immune cells in inflamed mouse joints. Synovitis, bone loss and matrix destruction are markedly reduced in Dcstamp-/-;Tg(hTNF) mice. These mice had significantly lower CCL2 and murine TNF serum levels and exhibited impaired monocyte joint migration compared to Tg(hTNF) mice. The reduced arthritic severity in Dcstamp deficient mice was associated with compromised monocyte chemotaxis, cytokine production, and M2 polarization. These results reveal that DC-STAMP modulates both bone resorption and inflammation and may serve as an activity biomarker and therapeutic target in inflammatory arthritis and metabolic bone disease.

Serum Markers CA125, CA153, and CEA along with Inflammatory Cytokines in the Early Detection of Lung Cancer in High-Risk Populations.

Lung cancer mortality and morbidity rates are the first among malignant tumors. It is extremely crucial to pay more attention to the early diagnosis and treatment of lung cancer and to grasp and judge the progress of the patient's condition promptly. In this study, lung cancer patients' early diagnosis with tumor markers and inflammatory variables is examined. The general surgery department of our hospital treated 98 patients with lung cancer and 100 patients with benign pulmonary hyperplasia from January 2017 to February 2018. Additionally, 100 healthy subjects who completed physical examinations during this time period were included. Based on the findings of the pathological examination, 100 patients with benign pulmonary hyperplasia were chosen as the benign group, 100 patients with lung cancer were chosen as the malignant group, and 100 healthy individuals were chosen as the healthy group. The tumor markers carbohydrate antigen 125 (CA125), CA153, and carcinoembryonic antigen (CEA), as well as inflammatory factors such as tumor necrosis factor- (TNF-) and high-sensitivity C-reactive protein, were measured in the venous blood of three groups of patients (hs-CRP). There was no discernible difference in tumor marker levels between the benign and healthy groups (P > 0.05). In comparison to the benign and healthy groups, the malignant group had higher serum levels of CA153, CA125, and CEA (P 0.05). Between the benign and healthy groups, there was no discernible difference in the levels of inflammatory factors (P > 0.05). TNF- and hs-CRP serum levels were observed to be higher in the malignant group compared to the benign and healthy groups (P 0.05). The combined detection of CA153 + CA125 + CEA + TNF − +hs − CRP showed the highest sensitivity and specificity, which were, respectively, 62.22 percent and 92.00 percent, when compared to single or mixed detection of tumor markers or inflammatory factors solely. Serum levels of inflammatory agents TNF- and hs-CRP may be related to the pathophysiology and other functions of patients with lung cancer, as well as to the development and metastasis of the disease. These markers include CA153, CA125, and CEA. For the early detection of lung cancer and the evaluation of the disease's severity, the detection of tumor markers in combination with inflammatory variables has a significant reference value.

Role of TNF and Hs CRP as novel biomarkers in etiopathogenesis of depression: A case-control study

Depression is a psychiatric disorder characterized by depressed mood, loss of interest in activities and loss of energy that lasts for two weeks or more. Depression affects individual emotional and psychological well-being with low self-esteem and ultimately resulted in social isolation. Nearly half of all cases of depression remain undetected for years or inadequately controlled. TNF-α has a vital role in inflammation, cell proliferation, differentiation, apoptosis, innate and adaptive immunity and have pathological role in several diseases. Early assessment of TNF-α and hs-CRP levels in depression patients could modify the disease progression and limit co-morbidities associated with it. Therefore, we assessed the level of TNF-α and hs-CRP in our study and correlated it with the disease severity.: to study is to estimate TNF-α and hs-CRP levels in depressed patients and evaluate the relationship between the serum level of TNF- α and hs-CRP in the etiopathogenesis of depression. This study was conducted at a tertiary level post graduate teaching institute of central India. 50 newly diagnosed drug naive cases of depression of age group 18-50 years, attending Psychiatry OPD. And 50 apparently healthy controls matched for same age and sex were taken. The subjects were enrolled for the study after taking ethics committee approval and obtaining written consent. The data collected was expressed as mean ± SD and analysed by using SPSS version 20. P-value of < 0.05 was accepted as statistically significant. The mean value of serum TNF-α among control group (11.209 ± 6.058 Pg/ml) which was lower as compared to case group (33.816 ± 21.581 Pg/ml). The difference among the two groups was found to be statistically significant as p value is less than 0.001. The mean Serum hs-CRP concentration was found to be higher in case group (7.524 ± 1.842 mg/l) as compare to control group (3.720 ± 1.238 mg/l). The difference among the two groups was found to be statistically significant as p value is <0.05. The difference among the three groups was found to be statistically significant as p value is less than 0.001. We observed a strong association between depression and increased serum TNF-α, with raised hs-CRP. There are several researches potentiating the vital role of TNF- α and hs-CRPin depression. Large scale prospective studies are needed to establish the cause effect relationship and role of inflammatory cytokines in depression and to find newer treatment modalities like TNF-α blockers that might be helpful for consideration of new therapeutic approach Further studies are essential to detect the association. Nevertheless we found that depression might be responsible for elevated TNF-α and hs-CRP levels. We suggest screening of all the patients of depression for serum TNF-α estimation at initial OPD visit.

Serum Levels of Intercellular Adhesion Molecule-1 and TNF- in Patients with COVID-19 and Its Relation to Disease Severity

Serum Levels of Intercellular Adhesion Molecule-1 and TNF- in Patients with COVID-19 and Its Relation to Disease Severity

Electrical Stimulation of the Dorsal Motor Nucleus of the Vagus Attenuates Serum Pro‐Inflammatory Cytokine Levels in Murine Models of Endotoxemia and Sepsis

The inflammatory reflex is a vagus nerve‐mediated and brainstem‐integrated physiological mechanism that regulates immunity and inflammation (Annu Rev Immunol, 2018, 36:783). The efferent vagus nerve originates in brainstem nuclei, including the dorsal motor nucleus of the vagus (DMN). Recently, it was shown that optogenetic stimulation of cholinergic DMN neurons inhibits serum TNF levels during endotoxemia (Proc Natl Acad Sci USA, 2020, 117(47):29803). However, the effects of electrical DMN stimulation on cytokine levels in inflammatory conditions have not been previously evaluated. To provide insight, we examined the effect of electrical DMN stimulation in mice with endotoxemia and cecal ligation and puncture (CLP)‐induced polymicrobial sepsis. In the endotoxemia model, 10–12‐week‐old male C57BL/6 mice (n=14‐20 per group) were anesthetized using isoflurane and the head was positioned on a stereotaxic frame. A surgical intervention and a stereotaxic‐guided approach were used to insert a concentric bipolar electrode into the left DMN. Electrical stimulation (50 μA, 30 Hz, 260 μs) or sham stimulation was performed for five mins, followed by lipopolysaccharide (LPS, 0.5 mg/kg) i.p. administration. The mice were euthanized 90 mins after LPS and blood (via cardiac puncture) was collected and processed for cytokine analysis. In the CLP model, DMN stimulation or sham stimulation was performed as described above immediately after subjecting mice (n=14‐20 per group) to CLP, i.e., following a midline laparotomy in anesthetised mice, the cecum was isolated and the distal end was ligated and punctured. 24h later, the mice were euthanised and blood was collected and processed for analysis. In mice with endotoxemia, electrical DMN stimulation significantly decreased serum TNF (p = 0.0069) and IL‐6 (p = 0.0427) levels compared with sham stimulation. In addition, electrical DMN stimulation increased the serum levels of the anti‐inflammatory cytokine IL‐10 (p = 0.0284). In mice with CLP, electrical DMN stimulation resulted in significantly lower serum TNF levels compared with sham stimulation (p = 0.0291). These results indicate for the first time that electrical DMN stimulation alters circulating pro‐inflammatory and anti‐inflammatory levels in murine endotoxemia and sepsis. These findings are of interest for further development of bioelectronic approaches targeting DMN for therapeutic benefit in conditions, characterised by immune dysregulation and inflammation.

Famotidine exerts anti‐inflammatory effects via a vagus nerve‐dependent mechanism

BackgroundThe COVID‐19 pandemic in the U.S. caused > 48 million infections and >500,000 deaths. Famotidine, a histamine H2 receptor antagonist widely used to treat acid reflux and gastritis, is associated with improved survival and attenuated COVID‐19 disease severity (Mather JF et al. Am J Gastroenterol. 115:1617,2020; Freedberg DE, et al. Gastroenterology 159: 1129, 2020; Janowitz T et al. Gut, 69:1592, 2020). However, the mechanism of action for these beneficial effects is unknown. As hyperactive inflammatory responses from SARS‐CoV‐2 plays a critical role in disease progression in COVID‐19, here we studied the effects of famotidine in murine models of cytokine storm.MethodsMale C57BL/6 mice were subjected to bilateral sub‐diaphragmatic vagotomy and were recovered for 7 days before experiments. Male C57BL/6 mice were given an injection of famotidine either intraperitoneally (4 mg/kg) or intracerebroventricular (0.4 mg/kg) prior to administration of LPS (7 mg/kg) given intraperitoneally. Mice were euthanized 2.5 hours after LPS administration and cytokine levels in sera were measured using ELISAs. For survival studies, male C57BL/6 mice were subjected to LPS (6 mg/kg) injected intraperitoneally followed by treatment with famotidine (intraperitoneal injection at 4 mg/kg) or vehicle (PBS) twice daily for 3 days, and survival was monitored for two weeks.ResultsFamotidine (4mg/kg, injected intraperitoneally at 30 min before LPS) significantly reduced LPS‐induced elevated serum TNF levels at 2.5 hours post‐LPS injection (serum TNF levels in LPS + vehicle = 1,491+ 129 vs. LPS + famotidine = 1,060 + 72* pg/ml, N=10 mice per group. *: P=0.001). Famotidine (4mg/kg, injected intraperitoneally, twice a day for 3 days) improved survival in endotoxemic mice (two‐week survival in famotidine group = 100% vs. 70% in the PBS‐control group, n=30/group, p=0.001). Famotidine administered intracerebroventricularly (0.4 mg/kg) also significantly reduced LPS‐induced serum TNF levels and was >10 times more potent via the intracerebroventricularly route as compared to the intraperitoneal route. Bilateral sub‐diaphragmatic vagotomy attenuated the cytokine inhibiting effects of famotidine (administered intracerebroventricularly) on LPS‐induced TNF release (serum TNF levels in LPS + vehicle = 592+ 55 vs. LPS + famotidine = 616 + 98 pg/ml, N=5 per group. P=N.S.).ConclusionsFamotidine stimulates vagus nerve’s inhibition of LPS‐induced TNF release and attenuates lethality in endotoxemic mice. These anti‐inflammatory effects require the intact vagus nerve and via a brainstem‐dependent mechanism.

Choline acetyltransferase attenuates inflammation in a murine model of DSS colitis and sepsis

Abstract Excessive immune cell activation and cytokine release leading to inflammatory conditions are associated with bidirectional immune system-brain communication and other physiological responses. The vagus nerve conveys sensory information to the brain and brain derived immunoregulatory signals suppressing peripheral cytokine levels and inflammation. Acetylcholine (A mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of choline acetyl transferase (ChAT), enzyme that catalyzes biosynthesis of acetylcholine, is unexplored. We studied the administration of ChAT in endotoxemia, sepsis and DSS colitis models. Intraperitoneal administration of ChAT significantly (p=0.002) suppresses serum levels of TNF (ChAT 1062.0pg/mL ± 113.0 vs vehicle 1711.0pg/mL ± 210.2) during murine endotoxemia. In a murine CLP sepsis model, administration of pegylated ChAT (PEG-ChAT) significantly improves survival (p=0.015), with a 55.6% survival in PEG-ChAT treated mice compared to a 22.2% survival in vehicle mice. In a preclinical model of inflammatory bowel disease, ChAT administration significantly improves body weight gain (d14 p=0.01 ChAT mice -5.1%±1.1 vs vehicle mice -15.5%±2.9), disease score (d11 p=0.006 ChAT mice 0.17DAI±0.05, vs vehicle mice 0.66DAI±0.13), and colon length (p=0.006 ChAT mice 7.15cm±0.2 vs vehicle mice 6.2cm±0.2) compared to vehicle. These results indicate that administration of ChAT inhibits TNF levels in acute endotoxemia and attenuates disease severity in murine models of sepsis and DSS-induced colitis, suggesting that further study of ChAT as an experimental anti-inflammatory therapeutic is warranted. Supported by grant from NIH to KJT and SSC.

The clinical differences between cough variant asthma cells and humoral immunology indicators.

The Purpose of this study was to study and analyze the clinical differences between cough variant asthma (CVA) cells and humoral immunology indicators. For this aim, 73 sick children with CVA were enrolled in this study and were admitted to the Pediatric Inpatient Department of Weifang Maternal and Child Health Hospital for treatment from April 2019 to May 2021. They were divided into the attack stage group (n=45) and the remission stage group (n=28). Meanwhile, 30 children with normal physical examination results were selected as normal controls. Differences in serum levels of TNF-, hs-CRP, IL-4, IL-5, IL-6 and IL-13 were compared among the three groups, as well as the differences in humoral immunology indicators such as T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/ CD8+ and IgA, IgG, IgG, IgM, IgE, IgE and IgG subtypes. Results showed that serum levels of TNF-α and hs-CRP were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The serum levels of TNF-α and hs-CRP were higher in the remission stage group than those in the normal control group, and the difference was not statistically significant (P>0.05). Serum levels of IL-4, IL-5, IL-6 and IL-13 were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). CD4+ and CD4+/CD8+ were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The difference in serum levels of IgG1, IgG2 and IgG3 was not statistically significant (P>0.05) among the three groups. While the level of IgG4 subsets in the attack stage group was significantly higher than that in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). Then the cytokines, cells and humoral immunology indicators of CVA patients are not in their normal range. They are involved in the pathogenesis of CVA. The combined detection is of great clinical significance in the diagnosis of early CVA to avoid misdiagnosis and missed diagnosis.

BONE TURNOVER IMBALANCE IN RHEUMATOID ARTHRITIS: RELATIONSHIP BETWEEN TUMOR NECROSIS FACTOR-α AND DICKKOPF-1 WITH BONE TURNOVER MARKERS

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to bone loss due to an imbalance of the bone turnover process that could be evaluated using bone turnover markers. Inflammation in RA is mainly mediated by Tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]) that will increase osteoclastogenesis. In recent studies, Dickkopf-1 (DKK-1) is a key regulatory pathway for bone formation that affects osteoblastogenesis. Objective: This study aims to examine the imbalance of the bone turnover process in RA patients. Methods: This was a cross-sectional study with 38 subjects of premenopausal women with RA. Serum levels of TNF-[Formula: see text], DKK-1, and bone turnover markers (CTx and P1NP) were investigated. Result: The median duration of RA in this study was 5 years with 60.5% of subjects in remission or with low disease activity. The median value of TNF-[Formula: see text] was 10.6 pg/mL, the mean value of DKK-1 was 4027[Formula: see text]pg/mL, the mean value of CTx was 2.74[Formula: see text]ng/mL, and the mean value of P1NP was 34[Formula: see text]pg/mL. This study revealed a weak positive correlation between TNF-[Formula: see text] and P1NP ([Formula: see text]; [Formula: see text]). Conclusion: This study found a low level of TNF-[Formula: see text], a high level of DKK-1, a high level of CTx and a low level of P1NP that indicates an imbalance of bone turnover process in RA patients that is in favor of bone resorption.

Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/\u03b2-catenin/RAS signaling pathway

BackgroundFibrosis is one of the most common pathological features of the aging process of the kidney, and fibrosis in aging kidneys also aggravates the process of chronic kidney disease (CKD). Corallodiscus flabellata B. L. Burtt (C. flabellata, CF) is a commonly used botanical drug in Chinese folklore. However, few studies have reported its pharmacological effects. This study aimed to explore the effect of CF ethanol extract on renal fibrosis in SAMP8 mice and identify potentially active compounds.MethodsSenescence-accelerated mouse-prone 8 (SAMP8) were used as animal models, and different doses of CF were given by gavage for one month. To observe the degree of renal aging in mice using β-galactosidase staining. Masson staining and the expression levels of Col-I, α-SMA, and FN were used to evaluate the renal fibrosis in mice. The protein expression levels of Nrf2 pathway and Wnt/β-catenin/RAS pathway in the kidney were measured. And β-galactosidase (β-gal) induced NRK-52E cells as an in vitro model to screen the active components of CF.ResultsThe CF ethanol extract significantly inhibited the activity of renal β-galactosidase and the expression levels of Col-I, α-SMA, and FN in SAMP8 mice, and improved Masson staining in SAMP8 mice. CF remarkably reduced urinary protein, creatinine, urea nitrogen and serum levels of TNF-α and IL-1β in SAMP8 mice, and significantly increased the levels of SOD and GSH-Px. Moreover, CF activated the Nrf2 pathway and blocked the Wnt/β-catenin/RAS pathway in the kidneys of mice. Besides, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated from CF, which reduced the senescence of NRK-52E cells, and maybe the active ingredients of CF playing the anti-aging role.ConclusionsOur experiments illuminated that CF ethanol extract may ameliorate renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS pathway. And SDC-0-14,16 and SDC-1-8 may be the material basis for CF to exert anti-renal senescence-related effects.

Relation of serum level of tumor necrosis factor-alpha to cognitive functions in patients with Parkinson\u2019s disease

BackgroundInflammation is suggested to play a role in the development of non-motor Parkinson’s disease (PD) symptoms. We aimed to investigate the association between serum tumor necrosis factor-alpha (TNF-α) levels and cognition in PD patients. Thirty patients with PD and 30 healthy controls were included. Evaluation and staging of PD were done using Unified PD Rating Scale. Cognitive assessment was done using Addenbrooke’s Cognitive Examination (ACE-III) and trail making B tests. Measurement of serum levels of TNF-α was done.ResultsPatients had significantly worser cognitive scores than controls except for language subclass of ACE score. Mean serum TNF-α level was significantly greater in PD patients as compared to controls. TNF-α serum level was significantly negatively correlated with ACE visuospatial function. Sensitivity and specificity of TNF-α to detect cognitive dysfunction in PD using ACE III and trail making B tests were (73.1, 75%), (57.1, 56.2%), respectively, whereas sensitivity and specificity of TNF-α to detect severity of PD using H&Y staging in PD were 50%.ConclusionPatients with PD frequently have cognitive impairment. Elevated serum TNF-α levels in patients with PD, and association of this cytokine to visuospatial impairment, implicate this pro-inflammatory cytokine in the neurobiology of cognitive impairment in PD.

Efficacy of Wumei Baijiang prescription on regulatory T cells / helper T cells Immune balance in mice with ulcerative coliti.

To observe the therapeutic effect of Wumei Baijiang prescription empirical prescription of Lu Zhizheng, on experimental ulcerative colitis (UC) mice, and to investigate the mechanism of the prescription in UC from the perspective of the immune balance of regulatory T cells (Treg) and helper T cells (Th17). Sixty C57BL/6 mice were randomly divided into 6 groups: normal group, model group, Chinese medicine group (high, medium and low dose group of Wumei Baijiang prescription) and control group (mesalazine sustained-release granules). Except for the normal group, the other groups used 2.5% dextran sulfate sodium to induce UC mice model. At the end of the model, the Chinese medicine group was given high, medium and low dose administration of Wumei Baijiang prescription, the control group was given slow-release granules of mesalazine, and the model group was given equal volume saline for 10 d. The changes of food intake, body weight, disease activity index (DAI) score, length of large intestine and histopathology were observed. The number of Treg, Th17, CD4+, CD8+ cells in spleen was detected by flow cytometry. The expression of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and C-reactive protein (CRP) in serum was detected by enzyme-linked immunosorbent assay. The middle and high-dose groups of Wumei Baijiang prescription were superior to the model group in terms of increasing food intake and body weight of colitis mice, restoring colon morphology, improving pathological damage, and reducing DAI (P < 0.05). There was no statistical difference with the mesalazine group (P > 0.05). Compared with the model group, the spleen Treg and CD4+ of the mice in the high and middle dose groups of Wumei Baijiang prescription were higher, while Th17 and CD8+ were lower (P < 0.05), and there was no statistical difference compared with the mesalazine group (P > 0.05). In addition, compared with the model group, the serum levels of TNF- and CRP in mice with high and middle doses of Wumei Baijiang prescription and mesalazine group were lower (P < 0.05), and IL-10 content was higher ( P < 0.05). Wumei Baijiang prescription can improve the general conditions of colitis mice, such as diarrhea, hematochezia, weight loss, and mucosal damage. The mechanism may be related to the regulation of Treg/Th17 immune balance.

The Potential of Serum IFN-γ for Determining the Progression of Chronic Hepatitis B

Background: A persistent infection of hepatitis B virus (HBV) can cause liver cirrhosis and hepatocarcinoma even though the virus itself is non-cytopathic and does not cause cell injury. It has been asserted that liver injury in chronic HBV infection is attributed to the host immune system responding to HBV infection. Cytokines have a critical role in mediating immune responses to viral infection. This study aimed to determine the correlation between the levels of serum IFN-γ, IL-2, IL-17, and TNF- α with the progress of chronic HBV infection that was determined through provisional diagnosis, patient’s age, and the levels of serum transaminases.Method: Blood samples were collected from patients with chronic hepatitis B and the levels of serum IFN-γ, IL-2, IL-17, and TNF-α were measured by using ELISA. The correlation between each cytokine levels and the provisional diagnosis, patient’s age, and serum transaminases were analyzed by using the Spearman correlation test with a p value of 0.05 is considered as statistically significant.Results: A total of 47 samples were collected from patients with chronic hepatitis B (n=38), chronic hepatitis B with liver cirrhosis (n = 6), and chronic hepatitis B with hepatocellular carcinoma (nc = 3). A significant correlation was found between the levels of serum IFN-γ and aspartate aminotransferase (AST) (p = 0.04).Conclusion: The increase of serum IFN-γ and AST levels may highlight the importance of these particular cytokine and liver transaminase in the immune response to chronic HBV infection since IFN-γ is capable to induce apoptotic cell death which promotes AST release and facilitates liver injury.

AN INDICATOR OF ACTIVE PULMONARY TUBERCULOSIS IN SERUM AS SERUM MACROPHAGE MIGRATION INHIBITORY FACTOR

Background: It has been demonstrated that the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which has chemokine-like properties, is a key player in a number of acute and long-term inflammatory disorders. However, nothing is known regarding the application of MIF as an inflammatory pathway marker in tuberculosis patients. The purpose of this study was to look at the relationship between MIF and IFN- and TNF-( relationship of MIF with IFN and TNF) in active pulmonary tuberculosis after anti-tuberculosis medication. Methods: By using cytokine-specific ELISA, the serum levels of MIF, TNF, and IFN were assessed in 40 patients with APTB at four different times: at baseline, 3, 5, and 7 months after starting anti-tuberculosis medication. Additionally, we assessed the serum levels of MIF, TNF, and IFN in 40 healthy controls. Results: Prior to the procedure, MIF serum levels were substantially higher (P&lt;0.04) in patients with APTB than in normal subjects, and high MIF levels (13.0 ng/mL) were linked to high TNF- α levels (449.6 pg/mL). Following 3, 5, and 7 months of treatment, MIF levels were considerably lowered (P&lt;0.02), with changes in TNF-α and IFNβ-serum levels. MIF levels and the paired TNF- level had a positive correlation at baseline (r=0.1102, P=0.0315) and after 7 months of treatment (r=0.09568, P=0.0363). Conclusion: After anti-tuberculosis therapy, a decrease in MIF serum levels in APTB patients might enhance the host immune system's defence against Mycobacterium tuberculosis infection. Therefore, serum MIF levels may serve as a helpful measure for evaluating the efficacy of medication in APTB patients.

Weaning Failure in Critically Ill Patients Is Related to the Persistence of Sepsis Inflammation.

Introduction: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. Methods: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. Results: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16–17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p < 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53–723, p = 0.023 and 0.3–64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: −17.6 to −4, p = 0.002). Conclusion: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed.

The Effectiveness of Chlorpromazine to Decrease the Level of Tumor Necrosis Factor-Alpha Serum in Schizophrenic Patients with Coronavirus Disease 2019

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2. The COVID-19 pandemic has also had an impact on mental health, including those with schizophrenia (SCH). There were 131 inpatient schizophrenic patients who were confirmed positive for COVID-19 at Dadi Makassar Hospital, South Sulawesi, Indonesia, but all of these patients did not experience any clinical symptoms of COVID-19. Chlorpromazine as an antipsychotic also has antiviral and anti-inflammatory effects in schizophrenic patients with COVID-19, and the schizophrenic neuroinflammatory is very likely to occur in patients with COVID-19 infection. AIM: The researchers tried to examine the effectiveness of chlorpromazine on serum TNF-values in schizophrenic patients with COVID-19. METHODS: This research is a nested case–control study. The study was conducted on schizophrenic patients with mild and asymptomatic cases of COVID-19 at Dadi Mental Hospital with a sample of 40 patients compared to 42 schizophrenic patients who were not COVID-19. Study subjects received chlorpromazine 100 mg/day for 4 weeks. Serum tumor necrosis factor-alpha (TNF-α) concentrations were measured by enzyme-linked immunosorbent assays when COVID-19 was first confirmed and after 4 weeks. Positive and negative syndrome scale (PANSS) and clinical global impression SCH (CGI-SCH) examinations were also performed to measure the clinical symptoms of SCH. RESULTS: The comparison of baseline TNF-serum levels that increased in the schizophrenic group with COVID-19 was 9.33 pg/ml higher, compared to the schizophrenic group without COVID-19. The decrease in TNF-levels in the schizophrenic group with COVID-19 of 7.96 pg/ml (p &lt; 0.001) indicated an improvement in TNF-serum levels at week 4. Meanwhile, there was no significant decrease in serum TNF- levels in the non-COVID-19 schizophrenic group (p &gt; 0.05). CONCLUSION: The serum TNF-value of schizophrenic patients with COVID-19 is higher than schizophrenic patients without COVID-19. Coadministration of chlorpromazine, antipsychotics, and COVID-19 therapy reduces serum TNF- values in schizophrenic patients with COVID-19. The administration of chlorpromazine and antipsychotic in therapeutic doses reduced the total PANSS and CGI-SCH values.

SERUM LEVEL OF IL-6, TNF-α, IL-4, IL-10 IN PATIENTS WITH CIRRHOSIS DUE TO CHRONIC HEPATITIS B

Objectives: This study was conducted to evaluate the serum level of interleukin - 6 (IL - 6), tumor necrosis factor α (TNF - α), interleukin - 4 (IL - 4) and interleukin - 10 (IL - 10) in a sample of patients affected by chronic HBV infection in various stage of liver cirrhosis to evaluate differences of the aforementioned cytokines between Child - Pugh classes, as well as between chronic hepatitis B (CHB)patients and healthy controls.Patients and methods: 78 chronic hepatitis B patients who were divided into three groups according to the Child - Pugh scoring system: group A comprised 24 patients with Child Pugh class A; group B comprised 39 patients with Child Pugh class B; and group C comprised 15 patients with Child Pugh class C. The study also included 10 healthy controls for comparing. Biochemical markers of liver disease were measured by clinical routine methods approved by IFCC. Serum concentrations of IL - 6, TNF - α, IL - 4, and IL - 10 were measured with the Human Cytokine/Chemokine ELISA Kit, Arigo Biolaboratories Corporation, Taiwan.Results: CHB patients showed statistically significant difference in TNF - α (p &lt; 0.001), IL - 4 (p &lt;0.01) and IL - 10 (p &lt; 0.01) levels versus healthy controls. Non-cirrhosis patients (Group A) showed statistically significant difference in TNF - α (p &lt; 0.001), IL - 10 (p &lt; 0.05) levels versus cirrhosis patients (Group B and C). Serum IL - 4 levels were significantly different between group B and group C patients (p &lt; 0.05). There was not any correlation between cytokines and biochemical markers of livercirrhosis.Conclusions: This study evaluated the serum cytokine levels (IL - 6, TNF - α, IL - 10, and IL - 4) of chronic hepatitis B patients, as well as the differences in such levels between patients and healthy controls. Although no correlations of cytokine levels with biochemical markers of liver disease were observed, serum levels of TNF - α, IL - 4, IL - 10 increase significantly in chronic hepatitis B patient, especially elevating in cirrhosis group (TNF - α, IL - 10); IL - 4 only increased in severe cirrhosis group (group C). TNF - α, IL - 4, IL - 10 but not IL - 6 may be a possible mediator in the pathogenesis of liver fibrosis.

L-carnitine ameliorates the muscle wasting of cancer cachexia through the AKT/FOXO3a/MaFbx axis

BackgroundRecent studies suggest potential benefits of applying L-carnitine in the treatment of cancer cachexia, but the precise mechanisms underlying these benefits remain unknown. This study was conducted to determine the mechanism by which L-carnitine reduces cancer cachexia.MethodsC2C12 cells were differentiated into myotubes by growing them in DMEM for 24 h (hrs) and then changing the media to DMEM supplemented with 2% horse serum. Differentiated myotubes were treated for 2 h with TNF-α to establish a muscle atrophy cell model. After treated with L-carnitine, protein expression of MuRF1, MaFbx, FOXO3, p-FOXO3a, Akt, p-Akt, p70S6K and p-p70S6K was determined by Western blotting. Then siRNA-Akt was used to determine that L-carnitine ameliorated cancer cachexia via the Akt/FOXO3/MaFbx. In vivo, the cancer cachexia model was established by subcutaneously transplanting CT26 cells into the left flanks of the BALB/c nude mice. After treated with L-carnitine, serum levels of IL-1, IL-6 and TNF-α, and the skeletal muscle content of MuRF1, MaFbx, FOXO3, p-FOXO3a, Akt, p-Akt, p70S6K and p-p70S6K were measured.ResultsL-carnitine increased the gastrocnemius muscle (GM) weight in the CT26-bearing cachexia mouse model and the cross-sectional fiber area of the GM and myotube diameters of C2C12 cells treated with TNF-α. Additionally, L-carnitine reduced the protein expression of MuRF1, MaFbx and FOXO3a, and increased the p-FOXO3a level in vivo and in vitro. Inhibition of Akt, upstream of FOXO3a, reversed the effects of L-carnitine on the FOXO3a/MaFbx pathway and myotube diameters, without affecting FOXO3a/MuRF-1. In addition to regulating the ubiquitination of muscle proteins, L-carnitine also increased the levels of p-p70S6K and p70S6K, which are involved in protein synthesis. Akt inhibition did not reverse the effects of L-carnitine on p70S6K and p-p70S6K. Hence, L-carnitine ameliorated cancer cachexia via the Akt/FOXO3/MaFbx and p70S6K pathways. Moreover, L-carnitine reduced the serum levels of IL-1 and IL-6, factors known to induce cancer cachexia. However, there were minimal effects on TNF-α, another inducer of cachexia, in the in vivo model.ConclusionThese results revealed a novel mechanism by which L-carnitine protects muscle cells and reduces inflammation related to cancer cachexia.

Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.