Effects Of Tumor Necrosis Factor-alpha Research Articles

The Effect of Inflammatory Status on Butyrate and Folate Uptake by Tumoral (Caco-2) and Non-Tumoral (IEC-6) Intestinal Epithelial Cells.

Objective Colorectal cancer (CRC) is the second leading cause of cancer death in occidental countries. Chronic inflammatory bowel disease (crohn’s disease and ulcerative colitis) is associated with an increased risk for CRC development. The aim of this work was to investigate the relationship between inflammatory status and absorption of nutrients with a role in CRC pathogenesis. Materials and Methods In this experimental study, we evaluated the in vitro effect of tumour necrosis factor-alpha (TNF-α), interferon-γ (IF-γ), and acetylsalicylic acid on 14C-butyrate (14C- BT), 3H-folic acid (3H-FA) uptake, and on proliferation, viability and differentiation of Caco-2 and IEC-6 cells in culture. Results The proinflammatory cytokines TNF-α and INF-γ were found to decrease uptake of a low concentration of 14C-BT (10 µM) by Caco-2 (tumoral) and IEC-6 (normal) intestinal epithelial cell lines. However, the effect of TNF-α and INF-γ in IEC-6 cells is most probably related to a cytotoxic and antiproliferative impact. In contrast, INF-γ increases uptake of a high concentration (10 mM) of 14C-BT in Caco-2 cells. The anticarcinogenic effect of BT (10 mM) in these cells is not affected by the presence of this cytokine. On the other hand, acetylsalicylic acid stimulates 14C-BT uptake by Caco-2 cells and potentiates its antiproliferative effect. Finally, both TNF-α and INF-γ cause a significant decrease in 3H-FA uptake by Caco-2 cells. ConclusionThe inflammatory status has an impact upon cellular uptake of BT and FA, two nutrients with a role in CRC pathogenesis. Moreover, the anti-inflammatory acetylsalicylic acid potentiates the anticarcinogenic effect of BT in Caco-2 cells by increasing its cellular uptake.

Effect of Tumor Necrosis Factor-Alpha on Erythropoietin and Erythropoietin Receptor-Induced Erythroid Progenitor Cell Proliferation in β-Thalassemia/Hemoglobin E Patients.

Objective:Thalassemia is one of the genetic diseases that cause anemia and ineffective erythropoiesis. Increased levels of several inflammatory cytokines have been reported in β-thalassemia and might contribute to ineffective erythropoiesis. However, the mechanism by which tumor necrosis factor-alpha (TNF-α) is involved in ineffective erythropoiesis in thalassemic patients remains unclear. The objective of this study is to investigate the effect of TNF-α on the erythropoietin (EPO) and erythropoietin receptor (EPOR) expression involved in proliferation of β-thalassemia/hemoglobin (Hb) E erythroid progenitor cells compared with cells from healthy subjects.Materials and Methods:CD34-positive cells were isolated from heparinized blood by using the EasySep® CD34 selection kit. Cells were then cultured with suitable culture medium in various concentrations of EPO for 14 days. The effect of TNF-α on percent cell viability was analyzed by trypan blue staining. In addition, the percentage of apoptosis and levels of EPOR protein were measured by flow cytometry.Results:Upon EPO treatment, a higher cell number was observed for erythroid progenitor cells from both healthy participants and β-thalassemia/Hb E patients. However, a reduction of apoptosis was found in EPO-treated cells especially for β-thalassemia/Hb E patients. Interestingly, TNF-α caused higher levels of cell apoptosis and lower levels of EPOR protein in thalassemic erythroid progenitor cells.Conclusion:TNF-α caused a reduction in the level of EPOR protein and EPO-induced erythroid progenitor cell proliferation. It is possible that TNF-α could be involved in the mechanism of ineffective erythropoiesis in β-thalassemia/Hb E patients.

Tumor Necrosis Factor-Alpha Gene Polymorphism Associated With Development of Hepatitis B Virus-associated Hepatocellular Carcinoma.

Host genetic diversity may play roles in development of HCC. This study was conducted to validate the effects of tumor necrosis factor-alpha (TNF-α) gene polymorphism on development of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV). The study cohort comprised 224 patients with HBV-associated HCC and 206 with HBV-associated liver cirrhosis (LC). Using chromosomal DNA, TNF-α promoter gene polymorphisms were determined at 3 common single-nucleotide polymorphism (SNP) sites (TNF-α-1031 T>C, TNF-α-857 C>T, and TNF-α-308 G>A) using a single base extension method. The genotype distributions were compared between the 2 groups. All the HBV-associated LC patients were followed up regularly every 6 to 12 months for surveillance of HCC development. In the cross-sectional analysis, the frequency of TNF-α-857 T allele was much higher in patients with HCC compared with those with LC (42% vs. 31%, P<0.01). Of 206 HBV-associated LC patients, 12 (5.8%) developed HCC during the median follow-up period of 36 months. The cumulative occurrence rates of HCC were significantly higher in patients with TNF-α-857 T allele than those withTNF-α-857 C/C genotype (1-, 3-, and 5-y rates: 2.9%, 12.8%, and 20.7% vs. 0%, 3.1%, and 5.3%, respectively; P=0.013). However, the other genetic polymorphisms of TNF-α promoter gene did not affect the development of HCC. In multivariate analysis, TNF-α-857 T allele was a significant predictor of HCC development (hazard ratio 6.29, P=0.01). Our data suggest that TNF-α-857 T allele is closely associated with development of HCC in HBV-associated LC patients.

Effect of Dexamethasone, LPS, or INFγ on the production of TNFα, IL-12, IL-6, IL-10, CXCL8, CXCL10, and CLC3, by bovine macrophages infected in vitro with Mycobacterium avium paratuberculosis.

Effect of Dexamethasone, LPS, or INFγ on the production of TNFα, IL-12, IL-6, IL-10, CXCL8, CXCL10, and CLC3, by bovine macrophages infected in vitro with Mycobacterium avium paratuberculosis.

Effect of tumour necrosis factor-alpha and interleukin-6 promoter polymorphisms on course of Crimean-Congo hemorrhagic fever in Turkish patients

Effect of tumour necrosis factor-alpha and interleukin-6 promoter polymorphisms on course of Crimean-Congo hemorrhagic fever in Turkish patients

Spectral domain-optical coherence tomographic findings in patients with ankylosing spondylitis under anti-tumor necrosis factor-alpha therapy

Objective: To evaluate the effect of tumor necrosis factor-alpha (TNF-α) blockade on the thickness of the peripapillary retinal nerve fiber layer (RNFL), the ganglion cell-inner plexiform layers (GCIPL), and the macula in ankylosing spondylitis (AS) patients under anti-TNF-α therapy.Materials and methods: Twenty-one patients with AS received etanercept, or adalimumab, or infliximab for at least 6 months. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were measured before and 6 months after the beginning of the treatment. Peripapillary RNFL, four regional fields (superior, inferior, nasal, and temporal), GCIPL, and macular thicknesses of the patients were analyzed by optical coherence tomography before the treatment, at 3 months and 6 months after the beginning of the treatment.Results: The mean BASDAI, ESR, and CRP values were 5.2 ± 1.5, 31.6 ± 21.7, and 15.7 ± 13.9, respectively, at the beginning of the treatment and 2.3 ± 1.7, 21.3 ± 15.1, and 10.1 ± 10.3, respectively, 6 months after the beginning of treatment. There were significant differences among the mean BASDAI, ESR, and CRP values at the beginning of treatment and 6 months later (p < 0.001, p = 0.007, and p = 0.009, respectively). There were no significant differences among peripapillary RNFL (p = 0.24), four regional fields (p = 0.98, p = 0.23, p = 0.09, p = 0.47), GCIPL (p = 0.25), or macular (p = 0.33) thicknesses of the patients during anti-TNF-α treatment. In addition, the mean intraocular pressure levels throughout the follow-up did not show significant variation on repeated-measures ANOVA (p = 0.77).Conclusions: TNF-α blockade does not seem to influence RNFL, GCIPL, or macular thickness of patients with AS in the short term.

Effects of tumor necrosis factor inhibitor on serum level of HLA-B27 and PDCD-1 in patients with ankylosing spondylitis.

The aim of this study was to evaluate the effect of tumor necrosis factor-alpha (TNF-α) inhibitor-infliximab on ankylosing spondylitis (AS) patients and detect the serum level of HLA-B27 and PDCD-1 before and after TNF inhibitor treatment. 138 patients at active stage of AS were treated with infliximab; serum was collected before and after TNF-α inhibitor treatment for analysis. Reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and enzyme-linked immuno sorbent assay were applied to detect the levels of HLA-B27 and PDCD-1 at different time points, which were used for statistical analysis with clinical data including two AS indicators (erythrocyte sedimentation rate--ESR and C-reactive protein--CRP). After the treatment for 6 weeks, RT-PCR showed that the gene expressions of HLA-B27 and PDCD-1 were significantly downregulated compared with baseline before infliximab treatment (P < 0.05); flow cytometry showed that the HLA-B27 and PDCD-1 double-labeled cells were significantly downregulated (P < 0.05). After 2, 6, or 10 weeks of infliximab treatment, the levels of ESR, CRP, serum HLA-B27, and PDCD-1 of the AS patients were all significantly lower than the baseline levels (P < 0.05), and the serum HLA-B27 and PDCD-1 levels were all significantly correlated with ESR (P < 0.05). Infliximab, an anti-TNF-α inhibitor, decreases significantly not only ESR and CRP, but also the serum levels of HLA-B27 and PDCD-1 in patients with AS. HLA-B27 and PDCD-1 are involved in the pathogenesis, and disease activities of AS. HLA-B27 and PDCD-1 are potentially the useful markers of AS activity and useful parameters to evaluate the effectiveness of anti-TNF-α inhibitor in treating AS.

SAT0343 Spinal Radiographic Progression during 6 Years of Tnf-Alpha Blocking Therapy in Patients with Ankylosing Spondylitis: Results from the GLAS Cohort

BackgroundSo far, inconsistent results have been reported regarding the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy on radiographic progression in ankylosing spondylitis (AS).ObjectivesTo prospectively investigate spinal radiographic progression up...

Clinical studies on bone-related outcome and the effect of TNF-α blocking therapy in ankylosing spondylitis

To provide an overview of clinical trials and observational studies investigating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone formation and bone loss in patients with ankylosing spondylitis (AS). The effect of TNF-α blocking therapy on excessive bone formation or osteoproliferation remains inconclusive. Radiographic assessment of spinal osteoproliferation is complicated by the overall slow rate of progression and the high variability between individual AS patients. Multiple studies demonstrated that TNF-α blocking therapy results in a significant increase in bone mineral density (BMD) at the lumbar spine and hip. Based on bone turnover marker (BTM) analysis, this can mainly be explained by an increase in mineralization and decrease in bone resorption. Both osteoproliferation (e.g. syndesmophytes and ankylosis of vertebrae) and excessive bone loss resulting in osteoporosis and vertebral fractures are frequently present in AS. Previous studies showed that BMD increases during TNF-α blocking therapy. Long-term follow-up in a large cohort of patients is needed to investigate whether TNF-α blockers can consolidate or stop spinal osteoproliferation and prevent vertebral fractures. Future studies should focus on the effect of these agents on bone-related outcome in AS patients with early vs. advanced disease.

An innovative three-dimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17

BackgroundAmong all cytokines involved in the pathogenesis and in the progression of psoriasis, Tumor Necrosis Factor (TNF)-alpha and interleukin (IL)-17 play a pivotal role. ObjectiveThe aim of the present study was to mimic a psoriatic microenvironment and to investigate the early effects of TNF-alpha and IL-17 in a three-dimensional model of organotypic normal human skin. MethodsHuman skin explants were obtained from plastic aesthetic surgery of healthy young women 20–40years old (n=7). The study was approved by the Institutional Review Board and written informed consent was obtained from all subjects. Bioptic fragments were cultured at the air–liquid interface overnight in a Transwell system and further divided before adding either 50ng/ml IL-17 or 100ng/ml TNF-alpha or a combination of both cytokines. For each subject, a control sample was cultured without any cytokine. Samples were harvested 24 or 48h after cytokine incubation. At both time points and for all cytokine treatments a bioptic fragment obtained from each patient was processed. Epidermal proliferation, expressions of terminal differentiation (keratin 10, K10, and 14, K14) and of intercellular adhesion (occludin for tight junctions and E-cadherin for adherens junctions) biomarkers were investigated by indirect immunofluorescence. ResultsIL-17 and TNF-alpha induced an early and statistically significant inhibition of keratinocyte proliferation (more than 80% compared with their respective controls). At 24h, the combination of both cytokines did not further reduce cell proliferation. Starting from 24h of incubation, a non-continuous occludin expression in the granular layer was observed after both IL-17 and TNF-alpha exposure. Immunolabelling for E-cadherin in adherens junctions, for K10 in the suprabasal layers, and for K14 in the basal layer was similar in all experimental groups and unaffected after cytokine treatment. ConclusionsThese results suggest that in this experimental model IL-17 and TNF-alpha induced an early alteration of the homeostasis of the inner proliferative layer and of the upper granular layer, as shown by cell proliferation inhibition and occludin expression.

Ligustilide prevents the apoptosis effects of tumour necrosis factor-alpha during C2C12 cell differentiation

Ligustilide, the major component of Angelica sinensis, is also thought to be the most potent bioactive constituent of this plant. Ligustilide has been reported to markedly protect neural tissue against apoptosis. However, little is known regarding ligustilide's anti-apoptosis effect in muscle tissue. The aim of the study was to investigate the anti-apoptosis effects of ligustilide on TNF-α-induced C2C12 cells during differentiation. It was revealed that ligustilide at various concentrations significantly prevented the apoptosis of C2C12 cells incubated in TNF-α as assessed by apoptosis index and DNA fragmentation. Moreover, ligustilide-treated groups exhibited a significant increase in the bcl-2/bax ratio, pro-caspase 3 and pro-caspase 8 compared with the TNF-α-control group in a dose-dependent manner. Meanwhile, ligustilide-treated groups presented a significantly increased level of phosphorylated Akt and suppressed expression of the myogenin protein. Therefore, the findings derived suggested that ligustilide protected C2C12 cells from TNF-α-induced apoptosis during differentiation by reducing apoptosis and inducing cell proliferation.

Exacerbation of recalcitrant cutaneous sarcoidosis with adalimumab - a paradoxical effect? A case report

The paradoxical adverse effects of tumor necrosis factor-alpha (TNF-alpha) antagonists have been described frequently as a result of the widespread use of these drugs. Among the TNF-alpha blocking agents, few reports exist relating the use of adalimumab in cutaneous sarcoidosis, although all of them show good results. More recently, sarcoidosis onsets have been reported with various TNF-alpha inhibitors. The current case is, to our knowledge, the first to describe the exacerbation of cutaneous lesions of sarcoidosis treated with adalimumab.

Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in rheumatoid arthritis (RA)

The biological properties of TNF-alpha make it a candidate therapeutic target in RA. Our studies have demonstrated that TNF-alpha and its receptors are up-regulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Neutralizing TNF-alpha antibodies reduce the production of the many pro-inflammatory cytokines, including IL-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF), produced by mononuclear cells from RA in culture. When injected into DBA/1 mice with collagen-induced arthritis and TNF-alpha transgenic mice with arthritis, anti-TNF MoAbs decrease inflammatory damage of joints. Clinical trials employing cA2, a chimaeric anti-TNF-alpha MoAb, in open-label and randomized placebo-controlled studies have demonstrated a dose-dependent efficacy with impressive improvement in disease activity and acute-phase responses lasting several weeks. We conclude that TNF-alpha is a critical mediator of inflammation in RA, and is an important therapeutic target in this disease.

Overexpressing TNF-Alpha in Pancreatic Ductal Adenocarcinoma Cells and Fibroblasts Modifies Cell Survival and Reduces Fatty Acid Synthesis via Downregulation of Sterol Regulatory Element Binding Protein-1 and Activation of Acetyl CoA Carboxylase

The effect of tumor necrosis factor-alpha (TNF-α) gene delivery has been suggested as a potentially useful therapeutic approach to improve the chemotherapeutic treatment of patients with pancreatic ductal adenocarcinoma (PDA), but the exact mechanism of its action is not clearly understood. In this study, we analyzed the expression profile of TNF-α in PDA tissue and explored its potential role in fatty acid synthase (FAS) regulation in PDA cells and in fibroblasts. Quantitative real-time polymerase chain reaction was used to examine the expression of TNF-α in PDA, matching adjacent tissues, and benign lesions. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan–Meier survival curves were generated. In vitro, we overexpressed the TNF-α gene in PDA cells and fibroblasts and analyzed its effect on cell survival, migration, and on members of the FAS signaling pathway. We also evaluated TNF-α effects on a panel of inflammation-, angiogenesis-, and metastasis-related markers. In the tumor tissue of PDA patients, compared with their matched adjacent tissue, expression levels of TNF-α were not statistically different and did not correlate with survival or any other examined clinicopathological features. Overexpression of TNF-α significantly (p < 0.05) reduced PDA and fibroblast cell migration. In PDA cells that highly overexpress TNF-α, this was associated with a significant reduction of FAS mRNA and protein expression levels and significant (p < 0.05) reduction of SREBP-1 and ACC mRNA. Reduction of FAS by TNF-α was inhibited when either SREBP-1 or ACC was knocked down by siRNA. PDA cells and fibroblasts that overexpress TNF-α displayed differential regulation of several inflammation-related markers and reduced levels of metastasis-related genes. Our data demonstrate a previously unknown multi-targeted involvement of TNF-α in PDA lipogenesis and inflammation and metastasis and suggest that intratumoral introduction of TNF-α may have the potential as a novel therapeutic approach in human PDA.

The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is associated with myocardial dysfunction observed in sepsis and septic shock. There are two fundamental components to this dysfunction. (1) systolic dysfunction; and (2) diastolic dysfunction. The aim of these experiments was to determine if any aspect of whole-heart dysfunction could be explained by alterations to global intracellular calcium ([Ca2+]i), contractility, and [Ca2+]i handling, by TNF-α, at the level of the individual rat myocyte. We took an integrative approach to simultaneously measure [Ca2+]i, contractility and sarcolemmal Ca fluxes using the Ca indicator fluo-3, video edge detection, and the perforated patch technique, respectively. All experiments were performed at 37°C. The effects of 50 ng/mL TNF-α were immediate and sustained. The amplitude of systolic [Ca2+]i was reduced by 31% and systolic shortening by 19%. Diastolic [Ca2+]i, myocyte length and relaxation rate were not affected, nor were the activity of the [Ca2+]i removal mechanisms. The reduction in systolic [Ca2+]i was associated with a 14% reduction in sarcoplasmic reticulum (SR) content and a 11% decrease in peak L-type Ca current (ICa-L). Ca influx was decreased by 7% associated with a more rapid ICa-L inactivation. These data show that at the level of the myocyte, TNF-α reduces SR Ca which underlies a reduction in systolic [Ca2+]i and thence shortening. Although these findings correlate well with aspects of systolic myocardial dysfunction seen in sepsis, in this model, acutely, TNF-α does not appear to provide a cellular mechanism for sepsis-related diastolic myocardial dysfunction.

THU0265 Early change in bone resorption predicts discontinuation of tumor necrosis factor-alpha blocking therapy in patients with ankylosing spondylitis

BackgroundIn ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking.ObjectivesTo investigate the predictive value of bone turnover markers (BTM) in relation to...

918 Overexpressing TNF-Alpha in Pancreatic Ductal Adenocarcinoma Cells and Fibroblasts Modifies Cell Survival and Reduces Fatty Acid Synthesis via Downregulation of Sterol Regulatory Element Binding Protein-1 and Activation of Acetyl CoA Carboxylase

The effect of tumor necrosis factor-alpha (TNF-α) gene delivery has been suggested as a potentially useful therapeutic approach to improve the chemotherapeutic treatment of patients with pancreatic ductal adenocarcinoma (PDA), but the exact mechanism of its action is not clearly understood. In this study, we analyzed the expression profile of TNF-α in PDA tissue and explored its potential role in fatty acid synthase (FAS) regulation in PDA cells and in fibroblasts. Quantitative real-time polymerase chain reaction was used to examine the expression of TNF-α in PDA, matching adjacent tissues, and benign lesions. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan–Meier survival curves were generated. In vitro, we overexpressed the TNF-α gene in PDA cells and fibroblasts and analyzed its effect on cell survival, migration, and on members of the FAS signaling pathway. We also evaluated TNF-α effects on a panel of inflammation-, angiogenesis-, and metastasis-related markers. In the tumor tissue of PDA patients, compared with their matched adjacent tissue, expression levels of TNF-α were not statistically different and did not correlate with survival or any other examined clinicopathological features. Overexpression of TNF-α significantly (p < 0.05) reduced PDA and fibroblast cell migration. In PDA cells that highly overexpress TNF-α, this was associated with a significant reduction of FAS mRNA and protein expression levels and significant (p < 0.05) reduction of SREBP-1 and ACC mRNA. Reduction of FAS by TNF-α was inhibited when either SREBP-1 or ACC was knocked down by siRNA. PDA cells and fibroblasts that overexpress TNF-α displayed differential regulation of several inflammation-related markers and reduced levels of metastasis-related genes. Our data demonstrate a previously unknown multi-targeted involvement of TNF-α in PDA lipogenesis and inflammation and metastasis and suggest that intratumoral introduction of TNF-α may have the potential as a novel therapeutic approach in human PDA.

Adalimumab (Humira) induced acute lung injury

Patient:Male, 78Final Diagnosis:Acute lung injury due to AdalimumabSymptoms:—Medication:AdalimumabClinical Procedure:Intubated and put on mechanical ventilationSpecialty:PulmonologyObjective:Unusual or unexpected effect of treatmentBackground:Adalimumab is a recombinant human monoclonal antibody that blocks the effects of tumor necrosis factor-alpha. Adalimumab related acute lung injury is a rare form of acute respiratory distress syndrome of possible immune etiology that develops immediately after an infusion.Case Report:We describe a 78 year old, male with no previous cardiac comorbidities, who developed acute lung injury (ALI) within one hour of administration of adalimumab. He was successfully treated with mechanical ventilatory support and adjuvant therapy.Conclusions:TNFα antagonists are a part of a new and revolutionary treatment for severe and difficult-to-treat autoimmune and inflammatory diseases. This report emphasizes that this fatal complication may occur with use of this drug. Clinicians need to be aware of this condition as prompt recognition and supportive management can prevent unwanted morbidity and mortality.

Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

The effect of tumor necrosis factor-alpha (TNF) on cyclooxygenase-2 (COX-2) expression in the renal outer medulla (OM) was determined in a model of dihydrotachysterol (DHT)-induced hypercalcemia. Increases in serum calcium and water intake were observed during ingestion of a DHT-containing diet in both wild type (WT) and TNF deficient mice (TNF−/−). Polyuria and a decrease in body weight were observed in response to DHT treatment in WT and TNF−/− mice. A transient elevation in urinary TNF was observed in WT mice treated with DHT. Moreover, increased urinary levels of prostaglandin E2 (PGE2) and a corresponding increase in COX-2 expression in the OM were observed in WT mice fed DHT. Increased COX-2 expression was not observed in TNF−/− mice fed DHT, and the characteristics of PGE2 synthesis were distinct from those in WT mice. This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent.

Early change in bone resorption predicts discontinuation of tumor necrosis factor-alpha blocking therapy in patients with ankylosing spondylitis

Background In ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking. Objectives To investigate the predictive value of bone turnover markers (BTM) in relation to discontinuation of TNF-α blocking therapy in patients with AS. Methods 111 consecutive AS outpatients from the Medical Center Leeuwarden and the University Medical Center Groningen who started TNF-α blocking therapy (infliximab n=22; etanercept n=71; adalimumab n=18) were included between November 2004 and December 2007. All patients fulfilled the modified New York criteria for AS (n=109) or the ASAS criteria for axial spondyloarthritis (n=2). Patients with recent fractures and/or use of bisphosphonates were excluded. Continuation of TNF-α blocking therapy was based on decrease in Bath AS Disease Activity Index (BASDAI) of at least 50% or 2 units compared with baseline, and/or expert opinion in favor of treatment continuation. Clinical assessments, marker of bone formation bone-specific alkaline phosphatase (BALP), and marker of bone resorption serum collagen-telopeptide (sCTX) were assessed at baseline, 3 and 6 months, and 1, 2, and 3 years. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group (200 men or 350 women) to correct for the normal influence that age and gender have on bone turnover. Results Mean age of the 111 AS patients was 42.2 years (SD ± 10.3), median disease duration was 16 years (range 1-49), and 70% were male. Mean BASDAI was 6.1 (SD ± 1.7) and mean AS disease activity index (ASDAS) was 3.8 (SD ± 0.8) at baseline. After 3 years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased BALP Z-score and significantly decreased sCTX Z-score compared to baseline. Baseline to 3 months decrease in sCTX Z-score (HR: 0.513, 95% CI: 0.367-0.717) was inversely associated with time to discontinuation of TNF-α blocking therapy in univariate Cox regression. Multivariate analysis showed that baseline to 3 months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263-0.591), ASDAS (HR: 0.488, 95% CI: 0.317-0.752), and physician’s global disease activity (GDA) (HR: 0.739, 95% CI: 0.600-0.909) were independent inversely related predictors of time to treatment discontinuation. Conclusions In addition to the ASDAS and physician’s GDA, early change in bone resorption marker sCTX after starting treatment can serve as an objective measure in the prediction of long-term continuation of TNF-α blocking therapy in AS. Disclosure of Interest None Declared