In Vivo Peripheral Blood Proinflammatory T Cells in Patients with Ankylosing Spondylitis

2012 ◽  
Vol 39 (4) ◽  
pp. 830-835 ◽  
Author(s):  
LEONARDO LIMÓN-CAMACHO ◽  
MARÍA INÉS VARGAS-ROJAS ◽  
JANITZIA VÁZQUEZ-MELLADO ◽  
JULIO CASASOLA-VARGAS ◽  
JOSÉ F. MOCTEZUMA ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Th1 Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Previous reports have shown an increase in peripheral blood mononuclear cells’ (PBMC) Th17 cell subpopulation and tumor necrosis factor-α (TNF-α) secretion after in vitro stimulation with anti-CD3/CD28 or phorbol myristate acetate/ionomycin in ankylosing spondylitis (AS). The aim of our study was to determine whether there is a Th17 polarization not subjected to in vitro stimulation in patients with AS.Methods.Nonstimulated PBMC were analyzed from 46 patients with AS, including 7 (15.2%) receiving tumor necrosis factor-α (TNF-α) inhibitors, 20 patients with rheumatoid arthritis, and 25 healthy controls. The surface phenotype of freshly isolated PBMC was determined by flow cytometry. Th1, Th2, Th17, and Treg subsets were defined as CD3+CD4+IFN-γ+, CD3+CD4+IL-4+, CD3+CD4+IL-17A+, and CD3+CD4+FoxP3+, respectively. Serum cytokines and interleukin 8 (IL-8) levels were quantified by Luminex technology.Results.The percentages of Th17 and Th1 cells in AS were higher than in healthy controls (7.4% ± 1.8% vs 0.7% ± 0.2% and 4.0% ± 1.3% vs 1.1% ± 0.3%, respectively; p < 0.0001). Th17 and Th1 cell subsets in patients taking TNF-α inhibitors were lower than in those naive to such therapeutics and similar to healthy controls. Serum levels of IL-6, IL-17A, TNF-α, and IL-8 were significantly higher in patients with AS compared to controls.Conclusion.The percentages of Th17 and Th1 cells in PBMC without in vitro stimulation, as well as cytokine and IL-8 levels, were significantly increased in patients with AS compared with healthy controls. These T cell subsets and cytokine profiles of patients with AS taking TNF-α inhibitors were similar to those of healthy controls.

scholarly journals Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5111-5120 ◽  
Author(s):  
Michael D. Milsom ◽  
Bernhard Schiedlmeier ◽  
Jeff Bailey ◽  
Mi-Ok Kim ◽  
Dandan Li ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Fanconi Anemia ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ectopic Expression ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

AbstractEctopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-α (TNF-α) signaling may be central to the self-renewal signature of HOXB4. Because HSCs derived from Fanconi anemia (FA) knockout mice are hypersensitive to TNF-α, we studied Fancc−/− HSCs to determine the physiologic effects of HOXB4 on TNF-α sensitivity and the relationship of these effects to the engraftment defect of FA HSCs. Overexpression of HOXB4 reversed the in vitro hypersensitivity to TNF-α of Fancc−/− HSCs and progenitors (P) and partially rescued the engraftment defect of these cells. Coexpression of HOXB4 and the correcting FA-C protein resulted in full correction compared with wild-type (WT) HSCs. Ectopic expression of HOXB4 resulted in a reduction in both apoptosis and reactive oxygen species in Fancc−/− but not WT HSC/P. HOXB4 overexpression was also associated with a significant reduction in surface expression of TNF-α receptors on Fancc−/− HSC/P. Finally, enhanced engraftment was seen even when HOXB4 was expressed in a time-limited fashion during in vivo reconstitution. Thus, the HOXB4 engraftment signature may be related to its effects on TNF-α signaling, and this pathway may be a molecular target for timed pharmacologic manipulation of HSC during reconstitution.

Dosage Adjustment of Anti-Tumor Necrosis Factor-α Inhibitor in Ankylosing Spondylitis Is Effective in Maintaining Remission in Clinical Practice

2012 ◽  
Vol 39 (7) ◽  
pp. 1418-1423 ◽  
Author(s):  
JULIEN PACCOU ◽  
MARIE-ASTRID BACLÉ-BOUTRY ◽  
ELISABETH SOLAU-GERVAIS ◽  
PEGGY BELE-PHILIPPE ◽  
RENÉ-MARC FLIPO
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Dosage Adjustment ◽  
Treatment Frequency ◽  
Response Predictors ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.While remission is possible in patients with ankylosing spondylitis (AS), it is often unclear what attitude should be adopted once remission has occurred. We investigated whether dosage adjustment is an effective means of maintaining remission.Methods.This was a retrospective study drawn from clinical situations. Remission was defined using clinical measures [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤ 20/100 and no peripheral joint disease] and biological measures [C-reactive protein (CRP) levels ≤ normal value]. The tumor necrosis factor-α (TNF-α) inhibitors used were infliximab, adalimumab, and etanercept. Response predictors of remission were evaluated by logistic regression (age, CRP, HLA-B27 positivity, sex, duration of disease, and anti-TNF-α naivety). CRP and BASDAI were evaluated before and after dosage adjustment at about 6, 12, 24, and 36 months.Results.One hundred eighty-nine patients with AS were included in the study, with a mean followup of 43.5 (± 17.9) months after the introduction of the first anti-TNF-α inhibitor. Mean age was 45.6 (± 12.5) years. Remission had occurred in 65 patients (35%). Significant response predictors of remission were male sex (p = 0.003) and anti-TNF-α naivety (p < 0.001). Dosage adjustment was observed 49 times, and progressively reducing treatment frequency was effective to maintain remission in a large number of patients for 36 months. The cumulative probability of continuing anti-TNF-α after dosage adjustment was 79.0% at 12 months, 70.5% at 24 months, and 58.8% at 36 months.Conclusion.Remission had occurred in 35% of the patients with AS under anti-TNF-α inhibitor therapy. Dosage adjustment and progressively reducing treatment frequency was effective in maintaining remission.

scholarly journals Dexamethasone Restores the Repressive Effect of Tumor Necrosis Factor-α on Follicular Growth and E2 Secretion During the In Vitro Culture of Preantral Follicles

2021 ◽  
Author(s):  
Que Wu ◽  
Tingwei Zhuang ◽  
Zhiling Li
Keyword(s):  
Tumor Necrosis Factor ◽  
In Vitro Culture ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Follicular Growth ◽  
Tnf Α ◽  
Repressive Effect ◽  
Factor Α ◽  
Necrosis Factor

AbstractAs a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) is central to the female reproductive tract and affects various phases of follicular development and uterine cycles. High levels of TNF-α play a vital role in the pathogenesis of polycystic ovary syndrome (PCOS) in patients. Clinicians know that dexamethasone can inhibit the induction of androgen by suppressing the adrenal glands which improves the status of the endocrine system in PCOS patients. We hypothesize that dexamethasone has much more functionality and can exert a therapeutic effect by antagonizing TNF-α. We added TNF-α to the follicular culture medium to simulate the high TNF-α levels observed in the endocrine environment of PCOS patients. Dexamethasone was added to the medium to determine if it could counteract the inhibitory effect of TNF-α on follicular growth and 17β-estradiol (E2) secretion. Follicular diameter, E2 concentration, follicle survival, antral-like cavity formation, and ovulation were measured to assess the effects of dexamethasone. In our work, TNF-α inhibited in vitro follicular growth and E2 secretion in a dose-dependent manner. Based on the results of the present research, we concluded that the addition of dexamethasone partially counteracts the repressive effect of TNF-α on follicle growth and E2 secretion during in vitro culture of the preantral follicles of mice. Thus, the findings in this paper suggest that dexamethasone may act as a therapy by counteracting the effects of TNF-α in PCOS patients. These results provide a new foundation for exploring the treatment of PCOS patients with dexamethasone.

scholarly journals Association of adipokines, interleukin-6, and tumor necrosis factor-α concentrations with clinical characteristics and presence of spinal syndesmophytes in patients with ankylosing spondylitis: A cross-sectional study

2017 ◽  
Vol 45 (3) ◽  
pp. 1024-1035 ◽  
Author(s):  
Laura Gonzalez-Lopez ◽  
Nicte S. Fajardo-Robledo ◽  
A. Miriam Saldaña-Cruz ◽  
Inocente V. Moreno-Sandoval ◽  
David Bonilla-Lara ◽  
...  
Keyword(s):  
Body Composition ◽  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Clinical Characteristics ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Serum Leptin ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective To identify correlations of the serum leptin, adiponectin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations with the clinical characteristics, presence of spinal syndesmophytes, and body composition in patients with ankylosing spondylitis (AS). Methods Forty-eight patients with AS were compared with 41 sex- and age-matched controls. Assessment included clinical characteristics and the presence of spinal syndesmophytes. The serum leptin, adiponectin, TNF-α, and IL-6 concentrations were determined. Body composition was evaluated using dual-energy X-ray absorptiometry. Results Patients with AS and controls had similar fat mass and lean mass. Patients with AS had higher serum TNF-α and leptin concentrations than controls (52.3 vs. 1.5 pg/mL and 17.2 vs. 9.0 µg/mL, respectively). The IL-6 and adiponectin concentrations were not significantly different between the two groups. Patients with syndesmophytes had higher leptin concentrations than those without syndesmophytes (22.1 vs. 10.9 µg/mL); this difference remained after adjustment for the body mass index. Conclusion Elevated leptin concentrations are associated with spinal radiographic damage in patients with AS and can serve as a biomarker. Future studies should evaluate whether leptin might be a potential target for treatments to avoid structural damage.

The Regulation of Platelet Aggregation In Vitro by Interleukin-1 β and Tumor Necrosis Factor-α: Changes in Pregnancy and in Pre-eclampsia

1997 ◽  
Vol 78 (04) ◽  
pp. 1255-1261 ◽  
Author(s):  
J Bar ◽  
A Zosmer ◽  
M Hod ◽  
M G Elder ◽  
M H F Sullivan
Keyword(s):  
Platelet Aggregation ◽  
Tumor Necrosis Factor ◽  
Pregnant Women ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Aggregation Of Platelets ◽  
Necrosis Factor

SummaryPlatelet activation occurs in early pregnancy in women at risk of developing pre-eclampsia. Cytokines have been implicated in the pathogenesis of pre-eclampsia, so we determined the effects of interleukin- 1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the in vitro aggregation of human platelets. IL-1β increased aggregation of platelets from non-pregnant and pre-eclamptic women, and inhibited the aggregation of platelets from normal pregnant women. This latter effect was linked to a diminished P-selectin expression on ADP-stimulated whole blood platelets in normal pregnant women (p = 0.011). Platelet aggregation in response to ADP was found to be inhibited after preincubation with TNF-α in non-pregnant (38%, p = 0.01) and in normal pregnant women (54%, p = 0.001) and not affected in pre-eclamptic women. The inhibitory effects of TNF-α were mediated through the P75 receptor for TNF-α.

scholarly journals Polymorphisms of the tumor necrosis factor-α gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2263-2265 ◽  
Author(s):  
Kai Neben ◽  
Joannis Mytilineos ◽  
Thomas M. Moehler ◽  
Astrid Preiss ◽  
Alwin Kraemer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gene Promoter ◽  
Nucleotide Polymorphisms ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-α (TNF-α) in vitro. We studied single nucleotide polymorphisms at positions −308 and −238 of the TNF-α gene promoter and measured the corresponding TNF-α cytokine levels in 81 patients (pts) with refractory and relapsed multiple myeloma (MM) who were treated with Thal. In myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with higher pretreatment TNF-α levels in peripheral blood (P = .047). After Thal administration, this TNF-238A group had a prolonged 12-month progression-free and overall survival of 86% and 100% versus 44% and 84% (P = .003 andP = .07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-α gene can affect TNF-α production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as “high producers” of TNF-α.

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