scholarly journals Establishment of a consistent L929 bioassay system for TNF-α quantitation to evaluate the effect of lipopolysaccharide, phytomitogens and cytodifferentiation agents on cytotoxicity of TNF-α secreted by adherent human mononuclear cells

2001 ◽  
Vol 10 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Ming-Yuh Shiau ◽  
Hui-Ling Chiou ◽  
Yao-Ling Lee ◽  
Tzer-Min Kuo ◽  
Yih-Hsin Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Hexamethylene Bisacetamide ◽  
Bioassay System ◽  
Human Mononuclear Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α ) plays an important role in the pathogenesis of rheumatoid arthritis. The present study was to evaluate the effects of lipopolysaccharide (LPS), phytomitogens and cytodifferentiation agents on cytotoxicity of TNF-α secreted by adherent human mononuclear cells (AMC). TNF-α cytotoxicity in LPS-treated, phytomitogen-treated, and cytodifferentiation agent-treated AMC supernatants were analyzed by the L929 bioassay system. Our results showed that LPS could induce homogeneous TNF-α production by AMC whereas, in addition to TNF-α, phytomitogens could also induce other TNF-like factors. Neither methotrexate, retinoic acid nor sodium butyrate can inhibit TNF-α cytotoxicity, while hexamethylene bisacetamide could not only inhibit TNF-α cytotoxicity but also TNF-α inducing ability of LPS to AMC.

TUMOR NECROSIS FACTOR-α CONVERTING ENZYME EXPRESSION IN THE JOINTS OF RHEUMATOID ARTHRITIS PATIENTS

2002 ◽  
Vol 06 (02) ◽  
pp. 63-71 ◽  
Author(s):  
Koichiro Takahi ◽  
Tetsuya Tomita ◽  
Takanobu Nakase ◽  
Motoharu Kaneko ◽  
Hiroshi Takano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Subchondral Bone ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The purpose of this study is to investigate the expression of tumor necrosis factor-α converting enzyme (TACE) in the synovium and subchondral bone region of patients with rheumatoid arthritis (RA) and to determine the contribution of the enzyme to the pathogenesis of RA. Joint tissues were obtained during total knee arthroplasty from patients with RA and osteoarthritis (OA). The expression of TACE and TNF-α mRNA was detected by in situ hybridization. Characterization of TACE expressing cells was performed by immunohistochemistry using serial sections. We found that TACE mRNA was expressed in both synovium and subchondral bone region and co-localized with TNF-α mRNA in RA. On the other hand, TACE mRNA expression was scarcely detectable in OA samples. TACE was expressed in mononuclear cells, such as CD3 and CD14 positive cells in RA samples. In conclusion, the expression of TACE is up-regulated in the rheumatoid synovium and subchondral bone region, and the results in this study demonstrate that TACE may be involved and play a role in the pathogenesis of RA.

scholarly journals Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

2002 ◽  
Vol 11 (5) ◽  
pp. 325-328 ◽  
Author(s):  
E. Jablonska
Keyword(s):  
Interleukin 6 ◽  
Polymorphonuclear Leukocytes ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Factor Α ◽  
Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

Tumor Necrosis Factor-α Inhibitor Use Is Not Associated with Lipid Changes in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 946-948 ◽  
Author(s):  
ANDRONIKI BILI ◽  
STEPHANIE J. MORRIS ◽  
JENNIFER A. SARTORIUS ◽  
H. LES KIRCHNER ◽  
JANA L. ANTOHE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Levels ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.To determine the association of use of tumor necrosis factor-α (TNF-α) inhibitors with differences in lipid levels in patients with rheumatoid arthritis (RA).Methods.We studied 807 patients with incident RA to compare differences in lipid levels in TNF-α inhibitor users versus nonusers, with adjustment for relevant covariables.Results.TNF-α inhibitor use was not associated with differences in levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or TC:HDL compared to nonusers.Conclusion.Use of TNF-α inhibitor was not associated with differences in lipid levels in patients with RA.

scholarly journals Granuloma Annulare: a Review of the Literature

2020 ◽  
Vol 24 (4) ◽  
pp. 410-415
Author(s):  
Tânia Aguiar Passeti ◽  
Wesley Pascoal Lisboa ◽  
Gabrielle Ellen Rodrigues Grinblat ◽  
Fernando Luiz Affonso Fonseca ◽  
Paulo Ricardo Criado ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Granuloma Annulare ◽  
Activation Patterns ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Granuloma annulare (GA) is a form of noninfectious skin granuloma, first described in 1895 as a rash in the form of a ring (annular), with regular, rounded edges. Around 50% of the cases are cured spontaneously within 2 years, however, a percentage of patients suffer from recurrent lesions or persistence for years. The pathogenesis of GA lesions is not well understood, with studies linking its expression to the presence of histocompatibility genes (HLA)-Bw35 or AH8.1 allele. These genes are related to the production of TNF-α (Tumor Necrosis Factor-α) by mononuclear cells. The pathogenesis includes the migration of macrophages to the dermis, the presence of cytokines, late hypersensitivity reaction, defects in regulating the neutrophil chemotaxis and degradation of the connective tissue. Its outbreak may be linked to predisposing factors, such as diabetes mellitus, thyroid changes and viral infectious diseases. The macrophages present in GA lesions may receive stimuli that result in its modulation to M1 or M2 activation patterns. The study of the M1 and M2 modulation mechanism in the lesion is important for an understanding of GA development.   Keywords: Granuloma Annulare. Macrophage. Immunology. Pathogenesis and Modulation.     Resumo O Granuloma Anular (GA) é um tipo de granuloma cutâneo não infeccioso, que foi descrito em 1895, como uma exantema em formato de anel (anular), de bordas regulares e arredondadas. Cerca de 50% dos casos têm cura espontânea em 2 anos, mas parte dos pacientes apresentam recidivas das lesões ou persistência por anos. A patogênese das lesões do GA é pouco conhecida. Estudos relacionam sua expressão à presença de genes de histocompatibilidade (HLA)-Bw35 ou AH8.1, que são relacionados à produção de TNF-α (Tumor necrosis factor - α), pelas células mononucleares. A patogênese também inclui migração de macrófagos para derme, presença de citocinas, reação de hipersensibilidade tardia, defeito na quimiotaxia de neutrófilos e degradação do tecido conectivo. O surgimento das lesões pode estar associado a fatores predisponentes, como diabetes mellitus, alterações tireoidianas e doenças infecciosas virais. Os macrófagos presentes nas lesões de GA podem sofrer estímulos que acarretem sua modulação para os padrões de ativação M1 ou M2. O estudo de tais mecanismo de modulação é importante para a compreensão da instalação e desenvolvimento do GA nos pacientes afetados.   Palavras-chave: Granuloma Anular. Macrófagos. Modulação. Imunologia e Patogênese.

scholarly journals Functional Analysis of a Human Tumor Necrosis Factor α (TNF-α) Promoter Polymorphism Related to Joint Damage in Rheumatoid Arthritis

1998 ◽  
Vol 4 (11) ◽  
pp. 724-733 ◽  
Author(s):  
Eric L. Kaijzel ◽  
Michiel V. van Krugten ◽  
Brigitta M. N. Brinkman ◽  
Tom W. J. Huizinga ◽  
Tahar van der Straaten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Joint Damage ◽  
Human Tumor ◽  
Promoter Polymorphism ◽  
Human Tumor Necrosis Factor ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α

2017 ◽  
Vol 36 (10) ◽  
pp. 2209-2216 ◽  
Author(s):  
Mohd Jahid ◽  
Rehan-Ul-Haq ◽  
Puja Kumari Jha ◽  
Diwesh Chawla ◽  
Rajnish Avasthi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies

2015 ◽  
Vol 42 (12) ◽  
pp. 2229-2237 ◽  
Author(s):  
Jing-Wen Ai ◽  
Shu Zhang ◽  
Qiao-Ling Ruan ◽  
Yi-Qi Yu ◽  
Bing-Yan Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Cohort Studies ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Tumor necrosis factor-α (TNF-α) antagonists have significantly improved treatment results in rheumatoid arthritis (RA), but have also increased the risk of tuberculosis (TB). Etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab, and certolizumab pegol are the 5 drugs currently available on the market. This article aimed to evaluate the risk of TB infection from these 5 drugs for patients with RA.Methods.We searched PubMed, EMBASE, COCHRANE library, OVID, and EBSCO for randomized controlled trials (RCT) of TNF-α antagonist versus control and registry/longitudinal cohort studies of 1 TNF-α antagonist versus another. The Mantel-Haenszel test was adopted to analyze risk ratio (RR) in this metaanalysis.Results.Fifty RCT and 13 non-RCT were included in this study. No significant difference in TB risk was found in the RCT because of the short observational periods. In the non-RCT, TNF-α antagonist was associated with a higher TB risk in patients with RA (RR 4.03, 95% CI 2.36–6.88), and the TB incidence rates of IFX and ADA were 2.78 and 3.88 times, respectively, higher than that of ETN. Further, preventive treatment for latent TB infection (LTBI) was shown to reduce the TB risk by 65% (RR 0.35, 95% CI 0.15–0.82).Conclusion.This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

Disease Activity Improvement in Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Inhibitors Correlates with Increased Soluble Fas Levels

2014 ◽  
Vol 41 (10) ◽  
pp. 1961-1965 ◽  
Author(s):  
Eloisa Romano ◽  
Riccardo Terenzi ◽  
Mirko Manetti ◽  
Francesca Peruzzi ◽  
Ginevra Fiori ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Soluble Fas ◽  
Tnf Α ◽  
Before And After ◽  
Factor Α ◽  
Necrosis Factor

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.

Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti–tumor necrosis factor-α antibody therapy

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Helen A. Papadaki ◽  
Heraklis D. Kritikos ◽  
Vasilis Valatas ◽  
Dimitrios T. Boumpas ◽  
George D. Eliopoulos
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Chronic Disease ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Anemia Of Chronic Disease ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Circumstantial evidence has implicated tumor necrosis factor α (TNF-α) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-α in erythropoiesis of patients with active RA (n = 40) and the effect of anti–TNF-α antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36−/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-α levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36−/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti–TNF-α antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-α on patients' erythropoiesis. We conclude that TNF-α–mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis.

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