scholarly journals CYCLOOXYGENASE MECHANISMS IN THE REGULATION OF RESPIRATORY EFFECTS OF TUMOR NECROSIS FACTOR

2019 ◽  
Vol 19 (1S) ◽  
pp. 17-17
Author(s):  
G A Danilova ◽  
A A Klinnikova ◽  
N P Aleksandrova

Introduction. It is known that the systemic level of the major pro-inflammatory cytokine increases in many respiratory diseases such as asthma, COPD and sleep apnea [1, 2]. The lung ventilation changes and the pathological types of breathing are typical in these diseases. By the reason, the research of the respiratory effects of cytokine is actual. The aim of this study was to compare the respiratory effects of tumor necrosis factor - α (TNF-α) before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Materials and methods. Тhe experiments were performed in tracheostomized anaesthetized with urethane rats. A respiratory flow head connected to a pneumotachometer (AD Instruments ML141 Spirometer, Dunedin, New Zealand) was used to measure peak airflow and respiratory rate. The hypoxic ventilatory response was measured by using rebreathing with hypoxic gas mixture before and after the tail vein injection of TNF-α (10 μg/rat). In order to determine the role of the cyclooxygenase pathway in the ventilatory effects of TNF-α, introperitoneal administration of diclofenac, a nonspecific COX inhibitor, was used (0.5 mg/rat). Results and discussion. We have shown that the increase in level of TNF-α in blood increased the parameters of respiration such as minute ventilation (by 40%), tidal volume (by 18%), and the mean inspiratory flow (by 33%). The slope of the hypoxic ventilatory response decreased from 6.06 ± 0.91 to 3.48 ± 0.38 ml/min-1 mmHg-1 (by 40%) 40 min after administration of TNF-α (p < 0.05), the slope of tidal volume and mean inspiratory flow also decreased (by 27%) (p < 0.05). After pretreatment with diclofenac, the influence of TNF-α on breathing was dampened, as no significant changes were observed. Conclusion. We concluded that the elevation of inflammatory cytokine level in blood intensifies ventilation during the resting breathing that may be associated with increased central inspiratory activity. At the same time TNF-α reduces the chemoreflex sensitivity to hypoxia, thereby worsening the compensatory capabilities of the respiratory system. Thus, the results of our study suggest participation of inflammatory cytokines in mechanisms of central breathing control and chemoreception. Diclofenac pretreatment eliminated the respiratory effects of TNF-α. The data indicate that the ability of TNF-α to enhance basal ventilation and to reduce the ventilatory hypoxic response is mediated by the COX pathway.

Author(s):  
Mohammad Daud Ali ◽  
Atul Kumar Gupta ◽  
Arif Naseer ◽  
Mohd Aamir Mirza ◽  
Sabir Afzal

 Objective: The main objective of this study was to assess tumor necrosis factor-α (TNF)-α and cyclooxygenase enzymes (COX) inhibition potency of Tamarindus indica Linn. in comparison to standard drug (indomethacin).Methods: Three plants are selected for the studies, namely: Aloe vera (L.), Terminalia chebula Reitz., and T. indica Linn. Estimation of TNF-α in serum (at 1:10 dilution in PBS) was performed using the immunoenzymatic (ELISA) technique. COX inhibitor screening assay kits were used for estimation of COX.Result: All three plant extracts showed a potent significant inhibition of the COX enzyme as compared to the positive control and standard drug when the animal was administered with 400 mg/kg. These studies indicate that the T. indica plant extract showed significant COX inhibition even at low dose. All the extracts were effective anti-inflammatory in nature, however, T. indica extracts at a dose of 400 mg/kg were found to be most potent. It was found to be comparable with that of Indomethacin 10 mg/kg body weight.Conclusion: The anti-inflammatory activity expressed by all the three plants A. vera (L.), T. chebula Reitz., and T. indica L. Among all three plants T. indica (L) was found to be more active against both TNF-α and COX, and it was comparable to standard drug Indomethacin. Need further studies to elucidate the exact secondary metabolite by which these plants express this activity.


2014 ◽  
Vol 41 (10) ◽  
pp. 1961-1965 ◽  
Author(s):  
Eloisa Romano ◽  
Riccardo Terenzi ◽  
Mirko Manetti ◽  
Francesca Peruzzi ◽  
Ginevra Fiori ◽  
...  

Objective.Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA by interfering with the Fas–Fas ligand (FasL) proapoptotic pathway. We investigated the circulating levels of soluble Fas (sFas) and soluble FasL (sFasL), and their possible correlation with disease activity and improvement after anti-TNF-α treatment in RA.Methods.Serum levels of sFas and sFasL were measured by quantitative ELISA in 52 patients with RA before and after 3 months of anti-TNF-α treatment (adalimumab, n = 32; infliximab, n = 20). Disease activity measures [Disease Activity Score at 28 joints-erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (CRP)] were recorded before and after treatment. Forty age-matched and sex-matched healthy subjects served as controls.Results.No significant differences in serum sFas levels were detected between anti-TNF-α-naive patients with RA and controls. After anti-TNF-α treatment, serum sFas levels significantly increased in patients with RA compared to both anti-TNF-α-naive patients and controls. Increased sFas levels inversely correlated with disease activity variables (DAS28-ESR: r = −0.739, CRP: r = −0.636, both p < 0.001). No significant differences in sFasL levels were detected in patients with RA before and after anti-TNF-α treatment.Conclusion.In RA, an increase in sFas levels closely correlates with improvement in disease activity induced by TNF-α inhibitors, suggesting their ability to modulate Fas-mediated synoviocyte apoptosis.


2021 ◽  
Author(s):  
G.А. Danilova ◽  
A.A. Klinnikova ◽  
N.P. Aleksandrova

At the present time very little is known about interactions between systemic inflammation and control of respiration. The aim of this study was to compare the respiratory effects of the main inflammatory cytokine TNF - α before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. In experiments on anesthetized, tracheostomized rats, pneumotachometry method was used to measure peak airflow and respiratory rate. The ventilatory response to hypoxia was investigated by the rebreathing method. It is shown that an increase in the systemic level of TNF – α causes a significant increase in the minute volume of respiration, tidal volume, the average speed of the inspiratory flow. In contrast the slope of the hypoxic ventilatory response decreased after administration of TNF-α. Diclofenac pretreatment eliminated these respiratory effects of TNF - α. The data indicate that the ability of TNF - α to enhance basal ventilation and to reduce the ventilatory hypoxic response is mediated by the cyclooxygenase pathway. Key words: tumor necrosis factor – α, hypoxia, prostaglandins, peripheral chemoreception, respiration.


2017 ◽  
Vol 1 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Ambarish Vijayaraghava ◽  
Venkatesh Doreswamy

Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were one of the first few cytokines to be discovered. The normative data for levels of cytokines IL-6 and TNF-α in particular and all other cytokines in general have not yet been established well. The normal levels for each of the cytokines vary from one race to another. Therefore, all studies need to be done in cases and controls belonging to the same race or same populations. The kits for cytokine assays are expensive and running the assays is laborious and time consuming. It is recommended that the serum/plasma samples are run in duplicates and triplicates to avoid error. Immunology and the field of cytokines is an area which has many domains unexplored. As yet, it is not clearly understood by what mechanisms and pathways each of the cytokines alter the levels of other cytokines. Exercise or physical activity is an intervention which can be administered easily and levels of cytokines measured before and after intervention in same individuals taking all the above mentioned factors into consideration. Hence it is imperative that we look into studies on exercise and cytokines to do further research in the field of cytokines.


2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.


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