scholarly journals Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis

2002 ◽  
Vol 196 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Hong Ji ◽  
Allison Pettit ◽  
Koichiro Ohmura ◽  
Adriana Ortiz-Lopez ◽  
Veronique Duchatelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Inflammatory Arthritis ◽  
Tumor Necrosis ◽  
Environmental Changes ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Tnf Α ◽  
Necrosis Factor

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)–α was also required, although seemingly less critically than IL-1, because a proportion of TNF-α–deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFα for bone destruction. The variability in the requirement for TNF-α, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

scholarly journals Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis

2020 ◽  
Vol 21 (11) ◽  
pp. 4145 ◽  
Author(s):  
Takahiko Akagi ◽  
Tomoyuki Mukai ◽  
Takafumi Mito ◽  
Kyoko Kawahara ◽  
Shoko Tsuji ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Tumor Necrosis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Ang Ii ◽  
Necrosis Factor ◽  
Systemic Bone Loss

Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.

scholarly journals Safety and Effectiveness of Rituximab in Patients with Rheumatoid Arthritis Following an Inadequate Response to 1 Prior Tumor Necrosis Factor Inhibitor: The RESET Trial

2011 ◽  
Vol 38 (12) ◽  
pp. 2548-2556 ◽  
Author(s):  
BOULOS HARAOUI ◽  
MARIA BOKAREWA ◽  
IAN KALLMEYER ◽  
VIVIAN P. BYKERK
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Patient Reported Outcomes ◽  
Tumor Necrosis ◽  
Primary Treatment ◽  
Tnf Α ◽  
Patient Reported ◽  
Infusion Reactions ◽  
Moderate Nausea ◽  
Necrosis Factor

Objective.To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated.Methods.In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment.Results.Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment.Conclusion.RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.

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 Biologic therapies for the treatment of rheumatoid arthritis

2021 ◽  
Vol 64 (2) ◽  
pp. 95-104
Author(s):  
Sung-Jae Choi
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Bone Destruction ◽  
Patient Characteristics ◽  
Necrosis Factor Alpha ◽  
Biological Products ◽  
Combined Use ◽  
Factor Alpha ◽  
Necrosis Factor

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. If left untreated, persistent synovial inflammation can lead to cartilage and bone destruction, ultimately causing significant longterm disability and mortality. However, since the late 1990s, the combined use of methotrexate, a synthetic diseasemodifying antirheumatic drug (DMARD), and a biological DMARD has revolutionized the treatment of RA. As of 2021, the Korea Food and Drug Administration has approved seven biological DMARDs for RA treatment: four tumor necrosis factor-alpha inhibitors (infliximab, etanercept, adalimumab, and golimumab) and three non-tumor necrosis factor biological products (abatacept, rituximab, and tocilizumab). Although the use of biological products has allowed significant advances in the treatment of RA, there are certain drawbacks, such as high cost, increased infection risk, and the necessity for parenteral route product administration. Therefore, discontinuation of biological DMARD use without a resulting disease flare is the next treatment goal and a desirable result from the standpoint of risk reduction and cost-effectiveness, especially for patients with clinical remission. It is still unclear which biological product is the best. Clinicians must, therefore, personalize the sequence and strategy of treatment by considering patient characteristics, disease activity, comorbidity, and economic condition

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.

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
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