Differential expression of TNF-α, IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium

2002 ◽  
Vol 282 (3) ◽  
pp. H926-H934 ◽  
Author(s):  
Emiliano A. Palmieri ◽  
Giulio Benincasa ◽  
Francesca Di Rella ◽  
Cosma Casaburi ◽  
Maria G. Monti ◽  
...  
Keyword(s):  
Time Course ◽  
De Novo ◽  
Mechanical Stretch ◽  
Progressive Increase ◽  
Compensatory Hypertrophy ◽  
Current Data ◽  
Rat Myocardium ◽  
Tnf Α ◽  
Normal Rat ◽  
Necrosis Factor

An isovolumic normal rat heart Langendorff model was used to examine the effects of moderate (15 mmHg) and severe (35 mmHg) mechanical stretch on the time course (from 0 to 60 min) of myocardial expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and insulin-like growth factor (IGF)-1 and their cognate receptors. After 10 min of moderate stretch, TNF-α was de novo expressed, whereas constitutive IL-6 and IGF-1 levels were slightly upregulated; no further changes occurred up to 60 min. In comparison, severe stretch resulted in a higher and progressive increase in TNF-α, IL-6, and IGF-1 expression up to 20 min. After 20 min, whereas TNF-α expression further increased, IL-6 and IGF-1 levels progressively reduced to values lower than those observed under moderate stretch and in unstretched (5 mmHg) control myocardium (IL-6). Mechanical stretch did not significantly alter the expression of the cognate receptors. Indeed, the TNF-α receptor (p55) tended to be progressively upregulated under severe stretch over time. The current data provide the first demonstration that TNF-α, IL-6, and IGF-1 ligand-receptor systems are differentially expressed within the normal rat myocardium in response to graded mechanical stretch. Such findings may have potential implications with regard to compensatory hypertrophy and failure.

scholarly journals The Prospects of tumor necrosis factor α inhibitors use in patients with COVID-19

2021 ◽  
Vol 15 (2) ◽  
pp. 89-93
Author(s):  
E. S. Aronova ◽  
B. S. Belov
Keyword(s):  
Clinical Trials ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Randomized Clinical Trials ◽  
Treatment Strategies ◽  
Current Data ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The review highlights the problem of finding new effective treatment strategies for COVID-19. Tumor necrosis factor α (TNF-α) is considered as a therapeutic target. The theoretical basis for the successful use of TNF-α inhibitors (ITNFα) for the treatment of COVID-19 is presented, as well as data on existing practical developments, including ongoing clinical trials. Two drugs from the group of ITNFα – infliximab and adalimumab – are currently being considered as possible options. The safety issues of ITNFα treatment in patients with immunophaling rheumatic diseases and COVID-19 are discussed. The review also provides current data on vaccination against COVID-19, in particular on the vaccines currently available in Russia, which are at different stages of clinical trials. We conclude that randomized clinical trials of the effectiveness and safety of ITNF-α in patients with the new coronavirus infection are needed. Such trials will promote transition from theoretical speculations to real clinical practice.

Involvement of brain cytokines in zymosan-induced febrile response

2014 ◽  
Vol 116 (9) ◽  
pp. 1220-1229 ◽  
Author(s):  
Amanda L. Bastos-Pereira ◽  
Daniel Fraga ◽  
Daniela Ott ◽  
Björn Simm ◽  
Jolanta Murgott ◽  
...  
Keyword(s):  
Time Course ◽  
Calcium Concentration ◽  
Febrile Response ◽  
Tnf Α ◽  
Heat Conservation ◽  
The Central Nervous System ◽  
Factor Α ◽  
The Brain ◽  
Circulating Levels ◽  
Necrosis Factor

This study compared the involvement of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) within the central nervous system (CNS) in the febrile response induced by zymosan (zym) and lipopolysaccharide (LPS). In addition, we investigated whether zym could activate important regions related to fever; namely, the vascular organ of the laminae terminalis (OVLT) and the median preoptic nucleus (MnPO). Intraperitoneal injection of zym (1, 3, and 10 mg/kg) induced a dose-related increase in core temperature. Zym (3 mg/kg) also reduced tail skin temperature, suggesting the activation of heat conservation mechanisms, as expected, during fever. LPS increased plasma levels of TNF-α measured at 1 h, IL-1β measured at 2 h, and IL-6 measured at 3 h after injection. Zym increased circulating levels of IL-6 but not those of TNF-α or IL-1β at the same time points. In addition, an intracerebroventricular injection of antibodies against TNF-α (2.5 μg) and IL-6 (10 μg) or the IL-1 receptor antagonist (160 ng) reduced the febrile response induced by zym and LPS. Zym (100 μg/ml) also increased intracellular calcium concentration in the OVLT and MnPO from rat primary neuroglial cultures and increased release of TNF-α and IL-6 into the supernatants of these cultures. Together, these results suggest that TNF-α, IL-1β, and IL-6 within the CNS participate in the febrile response induced by zym. However, the time course of release of these cytokines may be different from that of LPS. In addition, zym can directly activate the brain areas related to fever.

LPS induces late cardiac functional protection against ischemia independent of cardiac and circulating TNF-α

1997 ◽  
Vol 273 (4) ◽  
pp. H1894-H1902 ◽  
Author(s):  
Xianzhong Meng ◽  
Lihua Ao ◽  
James M. Brown ◽  
Daniel R. Meldrum ◽  
Brett C. Sheridan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Time Course ◽  
De Novo ◽  
Ischemia Reperfusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Isolated Hearts ◽  
Tnf Α ◽  
Peak Increase ◽  
De Novo Protein Synthesis ◽  
Lps Treatment

Lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α independently induce cardioprotection against ischemia in the rat at 24 h after administration, suggesting that endogenously synthesized TNF-α may play a role in LPS-induced protection. The purposes of this study were 1) to delineate the time course of LPS-induced cardiac functional protection against ischemia and its relation with myocardial and circulating TNF-α profile, 2) to examine whether prior protein synthesis inhibition abrogates the protection, and 3) to assess the effects of TNF-α inhibition and neutralization on the protection. Rats were treated with LPS (0.5 mg/kg ip). Cardiac functional resistance to normothermic global ischemia-reperfusion was examined at sequential time points after LPS treatment in isolated hearts by the Langendorff technique. Myocardial and circulating TNF-α was determined by enzyme-linked immunosorbent assay at 1–24 h after LPS treatment. Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide pretreatment (0.5 mg/kg ip 3 h before LPS treatment). Increases in myocardial and circulating TNF-α preceded the acquisition of protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg ip 30 min before LPS treatment) abolished peak increase in myocardial TNF-α and substantially suppressed circulating TNF-α (54.3 and 85.9% inhibition, respectively) without an influence on the maximal protection. Similarly, maximal protection was not affected by TNF binding protein (40 or 80 μg/kg iv immediately after LPS treatment). The results suggest that LPS-induced cardiac functional protection against ischemia is a delayed and long-lasting protective response that may involve de novo protein synthesis. Although LPS-induced increase in myocardial and circulating TNF-α precedes the delayed protection, it may not be required for the delayed protection.

scholarly journals POS1153 EFFECTIVENESS OF SCREENING IN PATIENTS WITH RHEUMATIC DISEASE ON BIOLOGICAL THERAPY AND RISK OF ACTIVE TUBERCULOSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 855.1-856
Author(s):  
S. Abdulaziz ◽  
S. Attar ◽  
W. Bajhammoh ◽  
E. A. Sindi ◽  
D. M. Ayish ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Biological Therapy ◽  
De Novo ◽  
Latent Tuberculosis ◽  
Biologic Therapies ◽  
Tnf Α ◽  
Latent Tb ◽  
Baseline Screening ◽  
Necrosis Factor ◽  
Tuberculosis Risk

Background:Treatment with biologic therapy has been associated with a high risk of reactivation of latent tuberculosis (TB). Preventive strategies for tuberculosis remain a crucial step before initiating biologics in rheumatic disease.Treatment with biological therapy has been associated with high risk of reactivation of latent tuberculosis (TB). Prevention strategies remain a crucial step before initiating biologics.Objectives:We aimed to assess the effectiveness of TB screening before the initiation of biologics and the risk of occurrence of active TB among patients with rheumatic diseases on biologic therapies.The study aimed to access the effectiveness of TB screening recommendations before the initiation of biological therapy and identify the incidence of active TB among these patients.Methods:We performed a hospital-based retrospective cohort study among rheumatic disease patients on biological therapy in two centers in Jeddah between January 2005 to December 2019. Medical files were retrospectively reviewed for demographics data, baseline screening for TB, use of prophylaxis, information on DMARDs and biological therapies, and outcomes results were collected.Results:A total of 365 patients were included over a period of 14 years. Two hundred ninety-two (80%) had Rheumatoid arthritis (RA),13% psoriatic arthritis (PSA), 9% spondyloarthritis (SPA), 2% SLE, and 4% others. The mean age was 47.54 (±14.2), 311 (85%) were females with a mean duration of disease 8.45 years (± 6.58). Hundred forty-nine (42.3%) were on steroids. Anti TNFs were prescribed in 213 (58.4%) patients, Non Anti-TNFs 124 (36.6%) patients, and Jak inhibitors 18 (5%) patients.TB screening was done to all patients except 3 patients (data missing) before commencing biologics. Forty-four (12.1%) patients had latent TB at baseline and all received chemoprophylaxis with isoniazid before starting biologics. Four patients with active TB were identified (one with Behcet’s disease and three with RA). One patient had a reactivation of latent TB and 3 patients developed de novo TB. Three out of four had an infection in the first 6 months of treatment (one on infliximab and two on rituximab) and one case after 1 year of stopping adalimumab. Two cases had pulmonary TB and two others with extrapulmonary TB (pericarditis and brain abscess each). All four patients with active TB were treated with standard anti TB medications. Three had complete resolution of their TB and one died.Conclusion:Baseline screening has been effectively carried out in our cohort as per recommendations. Physician should be vigilant not only for reactivation of latent TB but occurrence of de novo TB in patients on biological therapy.References:[1]Gardam, M. A. et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet. Infect. Dis.3, 148-155, doi:10.1016/s1473-3099(03)00545-0 (2003).[2]Winthrop, K. L., Yamashita, S., Beekmann, S. E. & Polgreen, P. M. Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network. Clin. Infect. Dis.46, 1738-1740, doi:10.1086/587989 (2008).[3]Cantini, F., Niccoli, L. & Goletti, D. Tuberculosis risk in patients treated with non-anti-tumor necrosis factor-α (TNF-α) targeted biologics and recently licensed TNF-α inhibitors: data from clinical trials and national registries. J. Rheumatol. Suppl.91, 56-64, doi:10.3899/jrheum.140103 (2014).Acknowledgements:We would acknowledge Dr. Noran Alhashmi, Dr. Roaa Jodah, and Dr. Lamis Ramadan for their assistance in data collection.Disclosure of Interests:None declared.

Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation

2002 ◽  
Vol 80 (1) ◽  
pp. 103-107 ◽  
Author(s):  
I Kimber ◽  
M Cumberbatch ◽  
R J Dearman ◽  
D R Headon ◽  
M Bhushan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Langerhans Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
De Novo ◽  
Intradermal Injection ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

It has been suggested previously that, in addition to other biological roles, lactoferrin (LF) may display anti-inflammatory properties secondary to the regulation of cytokine expression. To explore this concept further, we have here examined in human volunteers the influence of recombinant homologous LF on the migration of epidermal Langerhans cells (LC), a process that is known to be dependent upon the local availability of certain proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). In common with previous studies in mice, it was found that topical administration of LF prior to exposure at the same site to the contact sensitizer diphenylcyclopropenone resulted in a significant reduction of allergen-induced LC migration from the epidermis (measured as a function of the frequency of CD1a+ or HLA-DR+ LC found in epidermal sheets prepared from punch biopsies of the treated skin sites). However, under the same conditions of exposure, LF was unable to influence migration of LC induced by the intradermal administration of TNF-α data consistent with the hypothesis that one action of LF in the skin is to regulate the local production of this cytokine. Further support for this hypothesis was derived from experiments conducted with IL-1β. This cytokine is also able to induce the mobilization of LC following intradermal injection, although in this case, migration is known to be dependent upon the de novo production of TNF-α. We observed that prior exposure to LF resulted in a substantial inhibition of IL-1β-induced LC migration, data again consistent with the regulation of TNF-α production by LF. Collectively, these results support the view that LF is able to influence cutaneous immune and inflammatory processes secondary to regulation of the production of TNF-α and possibly other cytokines.Key words: lactoferrin, Langerhans cells, tumor necrosis factor α, interleukin 1β.

Effect of Blockade of Tumor Necrosis Factor-α with Etanercept on Surgical Wound Healing in SWISS-OF1 Mice

2009 ◽  
Vol 36 (10) ◽  
pp. 2144-2148 ◽  
Author(s):  
ESTIBALIZ IGLESIAS ◽  
FRANCISCO O’VALLE ◽  
JUAN SALVATIERRA ◽  
JOSE ANEIROS-FERNÁNDEZ ◽  
JESUS CANTERO-HINOJOSA ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Tumor Necrosis Factor Α ◽  
Healing Time ◽  
Surgical Wound ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.To assess whether blockade of tumor necrosis factor-α (TNF-α) influences surgical wound healing in a normal mouse experimental model.Methods.Wound healing time course and degree of surgical wound collagenization were measured by morphological techniques and digital image analysis in 80 male SWISS-OF1 mice (40 received subcutaneous etanercept at a dose of 0.1 mg/25g/ at −7, 0, 7, and 14 days).Results.No significant differences were observed between treated and untreated animals in wound healing, re-epithelialization, or formation of inflammatory infiltrate or granulation tissue at days 7, 15, or 20 after surgery. At 20 days, the collagen area was larger in treated versus untreated mice (109029 ± 28489 μm2 vs 79305 ± 19798 μm2, p = 0.026, Mann-Whitney U test).Conclusion.Surgical wounds showed a higher degree of collagenization at 20 days in etanercept-treated versus untreated mice, with no differences in the time course of wound healing. These data suggest that biological therapies to block TNF-α do not affect wound healing and do not need to be suspended during the perioperative period.

Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-α in normal rats

2003 ◽  
Vol 285 (6) ◽  
pp. R1402-R1409 ◽  
Author(s):  
Joseph Francis ◽  
Terry Beltz ◽  
Alan Kim Johnson ◽  
Robert B. Felder
Keyword(s):  
Mineralocorticoid Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Progressive Increase ◽  
Peripheral Tissues ◽  
Intracerebroventricular Infusion ◽  
Tnf Α ◽  
Factor Α ◽  
Circulating Levels ◽  
Necrosis Factor

Excessive mineralocorticoid receptor (MR) stimulation induces neurohumoral excitation and cardiac and vascular fibrosis. In heart failure (HF) rats, with excessive neurohumoral drive, central infusion of the MR antagonist spironolactone (SL) decreases blood-borne TNF-α. This study aimed to determine whether DOCA, a precursor of aldosterone, acts centrally to stimulate TNF-α production in normal rats. DOCA (5 mg sc daily for 8 days) induced a progressive increase in TNF-α beginning on day 3 and increased tissue TNF-α in hypothalamus, pituitary, and heart but not in other brain and peripheral tissues harvested on day 9. A continuous intracerebroventricular infusion of SL (100 ng/h) blocked the plasma TNF-α response. Oral SL (1 mg/kg) blocked the plasma and tissue TNF-α responses. Thus DOCA increases TNF-α in brain, heart, and blood in normal rats. Activation of brain MR appears to account for the increase in plasma TNF-α. These findings have important implications for the understanding of pathophysiological states (e.g., HF, hypertension) characterized by high circulating levels of aldosterone.

Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts

1999 ◽  
Vol 276 (6) ◽  
pp. H1968-H1976 ◽  
Author(s):  
Tomoyuki Yokoyama ◽  
Kenichi Sekiguchi ◽  
Toru Tanaka ◽  
Koichi Tomaru ◽  
Masashi Arai ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Mechanical Stress ◽  
Cardiac Myocytes ◽  
Tumor Necrosis ◽  
Cardiac Fibroblasts ◽  
Mechanical Stretch ◽  
Intracellular Camp ◽  
Ang Ii ◽  
Tnf Α ◽  
Necrosis Factor

To determine whether ANG II as well as mechanical stress affect the production of tumor necrosis factor (TNF) in the heart, neonatal rat cardiac myocytes and fibroblasts were cultured separately and treated for 6 h with ANG II, lipopolysaccharide (LPS), or cyclic mechanical stretch. LPS induced the production of TNF in cardiac myocytes and fibroblasts. However, TNF synthesis in fibroblasts was 20- to 40-fold higher than in myocytes. ANG II (≥10−8 M) and mechanical stretch stimulated the production of TNF in cardiac fibroblasts but not in myocytes. Furthermore, both ANG II and LPS increased the expression of TNF-α mRNA in cardiac fibroblasts. Isoproterenol inhibited both LPS- and ANG II-induced production of TNF in cardiac fibroblasts with increasing intracellular cAMP level. Moreover, both isoproterenol and dibutyryl cAMP inhibited LPS-induced TNF-α mRNA expression. Thus activation of the renin-angiotensin system, as well as mechanical stress, can stimulate production of TNF in cardiac fibroblasts. Furthermore, β-adrenergic receptors may be responsible for the regulation of TNF synthesis at the transcriptional level by elevating intracellular cAMP.

scholarly journals Baricitinib restrains the immune dysregulation in COVID-19 patients

2020 ◽  
Author(s):  
Vincenzo Bronte ◽  
Stefano Ugel ◽  
Elisa Tinazzi ◽  
Antonio Vella ◽  
Francesco De Sanctis ◽  
...  
Keyword(s):  
Small Molecules ◽  
Target Therapy ◽  
Serum Levels ◽  
Progressive Increase ◽  
Good Prognosis ◽  
Rapid Reduction ◽  
Jak2 Inhibitor ◽  
Immune Mediators ◽  
Tnf Α ◽  
Necrosis Factor

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing pandemic coronavirus disease 2019 (COVID-19). The majority of patients with COVID-19 have a good prognosis, but variable percentages in different countries develop pneumonia associated with lymphocytopenia and severe inflammatory response due to uncontrolled release of cytokines. These immune mediators are transcriptionally regulated by JAK-STAT molecular pathways, which can be disabled by small molecules. Here, we provide evidences on the efficacy of baricitinib, a JAK1/JAK2 inhibitor, in correcting the immune abnormalities observed in patients hospitalized with COVID-19. Indeed, we demonstrate a significant reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)α, a rapid recovery in circulating T and B cell frequencies and an increased antibody production against SARS-CoV-2 spike protein in baricitinib-treated patients. Moreover, treated patients underwent a rapid reduction in oxygen flow need and progressive increase in the P/F. Our work provides the basis on developing effective treatments against COVID-19 pathogenesis using on-target therapy.

scholarly journals Serum Cytokine Responses in Primary Pneumonic Plague Patients

2010 ◽  
Vol 18 (1) ◽  
pp. 184-186 ◽  
Author(s):  
Xiaoyi Wang ◽  
Zuyun Wang ◽  
Zhaobiao Guo ◽  
Baiqing Wei ◽  
Fuzhang Tian ◽  
...  
Keyword(s):  
Time Course ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Pneumonic Plague ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACTThe serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.

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