• Biologic therapy
• Cardiometabolic risk
• Cardiovascular disease
• HbA1c
• Lipids
• Metabolic syndrome
• Psoriasis
• Retrospective review

• Ankylosing spondylitis
• Dyslipidemias
• Inflammation
• Tumor necrosis factor inhibitors

• gestational diabetes mellitus
• inflammation
• oxidative stress
• physical activity
• type 2 diabetes mellitus

• inflammation
• joint destruction
• lipid metabolism
• rheumatoid arthritis
• treatment

• Humans
• Lipid Metabolism
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/drug therapy
• Arthritis, Rheumatoid
• Antirheumatic Agents/therapeutic use
• Lipids/therapeutic use

Adropin is a secretory protein that mainly modulates metabolic homeostasis and endothelial function. There is growing evidence supporting association of adropin with various inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to compare serum adropin levels between 70 patients with RA and 70 matched healthy controls. Furthermore, we explored adropin correlations with RA disease activity, glucose metabolism parameters and inflammatory biomarkers. Serum adropin levels were determined by a competitive enzyme-linked immunosorbent assay. Serum adropin levels were significantly lower in RA patients than in the control group (2.85 ± 0.91 vs. 4.02 ± 0.99 ng/mL, p < 0.001). In the RA group, serum adropin levels had a significant negative correlation with total cholesterol (r = −0.172, p = 0.043), HbA1c (r = −0.406, p < 0.001), fasting glucose (r = −0.377, p < 0.001) and HOMA-IR (the homeostasis model assessment-estimated insulin resistance; (r = −0.315, p = 0.008)). Multiple linear regression analysis showed that serum adropin levels retained a significant association with levels of fasting glucose (β ± SE, −0.450 ± 0.140, p = 0.002) and HbA1c (−0.528 ± 0.223, p = 0.021) after model adjustments. These findings imply that adropin could have an impact on metabolic homeostasis in RA, although further well-designed studies are warranted in order to establish this.

• high-density lipoprotein
• lipid
• meta-analysis
• rheumatoid arthritis
• tumor necrosis factor

• PACT
• PKR
• RIG-I-like receptors
• inflammasome
• inflammation
• metaflammation

• Humans
• Inflammation/metabolism
• RNA-Binding Proteins/metabolism
• Signal Transduction
• eIF-2 Kinase/metabolism

• R01 DK053307 NIDDK NIH HHS
• P30 DK097948 NIDDK NIH HHS
• R21 AI144264 NIAID NIH HHS
• R01 DK060596 NIDDK NIH HHS
• R01 DK113196 NIDDK NIH HHS
• R01 AI116730 NIAID NIH HHS
• R21 CA246194 NCI NIH HHS

Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.

• comorbidities
• extra-articular manifestations
• immunomodulation
• psoriatic arthritis
• psoriatic disease
• systemic inflammation

• BMI
• HDL-cholesterol
• LDL-cholesterol
• effect modification
• inflammation

• K24 AI143447 NIAID NIH HHS
• UH3 AI122309 NIAID NIH HHS

• Biological Products/pharmacology
• Biological Products/therapeutic use
• Comorbidity
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/immunology
• Humans
• Metabolic Syndrome/drug therapy
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/immunology
• Psoriasis/drug therapy
• Psoriasis/epidemiology
• Psoriasis/immunology
• Signal Transduction/drug effects
• Signal Transduction/immunology
• Treatment Outcome
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Tumor Necrosis Factor-alpha/metabolism

• diabetes
• interleukin 6
• myocardial infarction
• rheumatoid arthritis
• tumor necrosis factor α

• not receive funds

Like other autoimmune diseases, rheumatoid arthritis (RA) develops in distinct stages, with each phase of disease linked to immune cell dysfunction. HLA class II genes confer the strongest genetic risk to develop RA. They encode for molecules essential in the activation and differentiation of T cells, placing T cells upstream in the immunopathology. In Phase 1 of the RA disease process, T cells lose a fundamental function, their ability to be self-tolerant, and provide help for autoantibody-producing B cells. Phase 2 begins many years later, when mis-differentiated T cells gain tissue-invasive effector functions, enter the joint, promote non-resolving inflammation, and give rise to clinically relevant arthritis. In Phase 3 of the RA disease process, abnormal innate immune functions are added to adaptive autoimmunity, converting synovial inflammation into a tissue-destructive process that erodes cartilage and bone. Emerging data have implicated metabolic mis-regulation as a fundamental pathogenic pathway in all phases of RA. Early in their life cycle, RA T cells fail to repair mitochondrial DNA, resulting in a malfunctioning metabolic machinery. Mitochondrial insufficiency is aggravated by the mis-trafficking of the energy sensor AMPK away from the lysosomal surface. The metabolic signature of RA T cells is characterized by the shunting of glucose toward the pentose phosphate pathway and toward biosynthetic activity. During the intermediate and terminal phase of RA-imposed tissue inflammation, tissue-residing macrophages, T cells, B cells and stromal cells are chronically activated and under high metabolic stress, creating a microenvironment poor in oxygen and glucose, but rich in metabolic intermediates, such as lactate. By sensing tissue lactate, synovial T cells lose their mobility and are trapped in the tissue niche. The linkage of defective DNA repair, misbalanced metabolic pathways, autoimmunity, and tissue inflammation in RA encourages metabolic interference as a novel treatment strategy during both the early stages of tolerance breakdown and the late stages of tissue inflammation. Defining and targeting metabolic abnormalities provides a new paradigm to treat, or even prevent, the cellular defects underlying autoimmune disease.

• T cell
• autoimmunity
• fatty acid
• glutaminolysis
• glycolysis
• metabolism
• mitochondria
• rheumatoid arthritis

In addition to β-cell failure with inadequate insulin secretion, the crucial mechanism leading to establishment of diabetes mellitus (DM) is the resistance of target cells to insulin, i.e. insulin resistance (IR), indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor, downstream to the substrates of insulin action. IR is a common feature of most metabolic disorders, particularly type II DM as well as some cases of type I DM. A variety of human inflammatory disorders with increased levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, have been reported to be associated with an increased risk of IR. Autoimmune-mediated arthritis conditions, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with the involvement of proinflammatory cytokines as their central pathogenesis, have been demonstrated to be associated with IR, especially during the active disease state. There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders. In this review, we focus on the effects of anti-TNF-α- and non-TNF-α-targeted therapies on IR in patients with RA, PsA and AS. Anti-TNF-α therapy, IL-1 blockade, IL-6 antagonist, Janus kinase inhibitor and phospho-diesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

• Insulin resistance
• Diabetes mellitus
• Tumor necrosis factor-α-targeted therapy
• Non-tumor necrosis factor-α-targeted therapy
• Rheumatoid arthritis
• Psoriatic arthritis

• Abatacept
• IL inhibitor
• New-onset diabetes
• Rituximab
• TNF-α inhibitor
• bDMARD

Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes.

Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes.

Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was − 0.28 (− 0.40, − 0.16; nominal p <  0.0001) and − 0.42 (− 0.54, − 0.31; nominal p <  0.0001), respectively. Without csDMARDs, LS mean difference for sarilumab 200 mg vs. adalimumab 40 mg at week 24 was − 0.13 (− 0.22, − 0.04; nominal p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA.

In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings.

ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.

• Adalimumab
• Glycosylated haemoglobin
• IL-6
• Immuno-metabolism
• Inflammation
• Rheumatoid arthritis
• Sarilumab

Current evidence highlights a link between insulin resistance (IR) and disease activity in rheumatoid arthritis (RA), suggesting that insulin sensitivity can be improved by treating patients with TNF‐α blockers. Although reduced IR has been shown in RA patients who receive monoclonal antibody treatment, the efficacy remains to be elucidated when using recombinant soluble receptor fusion proteins. In particular, etanercept (ETA) is capable of blocking lymphotoxin‐α, a cytokine‐related to IR‐associated disease status.

A prospective study was carried out in nondiabetic active RA patients receiving a 25‐mg subcutaneous ETA injection twice weekly.

Thirty patients aged 31 to 73 years (50.9 ± 10.6), naïve to biological and targeted synthetic disease‐modifying antirheumatic drugs with DAS28 scores of 5.17 to 7.49 (6.11 ± 0.66), were classified into high‐IR and low‐IR groups based on their baseline homeostatic model assessment (HOMA)‐IR levels. No differences were found between the two groups in terms of age, sex, weight, body mass index, seropositivity, and medication profiles before the injection. After a 24‐week therapeutic period, there were reduced HOMA‐IR levels in all patients in the high‐IR group (3.390 ± 0.636 to 2.234 ± 0.870, P < 0.001). A greater decrease in DAS28 values was found in patients with reduced IR than those without a reduction (2.54 ± 0.67 versus 1.46 ± 0.46, P = 0.006) in the low‐IR group.

We observed an improvement in insulin sensitivity in nondiabetic active RA patients following 24‐week recombinant soluble TNF‐α receptor fusion protein therapy.

• Diabetes
• Disease-modifying anti-rheumatic drugs
• Glucocorticoids
• Meta-analysis
• Rheumatoid arthritis

• Corticosteroids
• Gastrointestinal Microbiome
• Glucose Homeostasis
• Inflammation
• Metabolic Disorder

• Adipokines
• TNF-α insulin resistance
• atherogenic index
• insulin sensitivity
• rheumatoid arthritis

• Adalimumab/administration & dosage
• Adalimumab/adverse effects
• Adipokines/blood
• Adipokines/classification
• Adult
• Antibodies, Monoclonal/pharmacology
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/metabolism
• Etanercept/administration & dosage
• Etanercept/adverse effects
• Female
• Humans
• Infliximab/administration & dosage
• Infliximab/adverse effects
• Insulin Resistance
• Lipid Metabolism/drug effects
• Male
• Middle Aged
• Severity of Illness Index
• Treatment Outcome
• Tumor Necrosis Factor Inhibitors/administration & dosage
• Tumor Necrosis Factor Inhibitors/adverse effects

• Adipokine
• Dyslipidemia
• Pathophysiology

• Adiponectin/metabolism
• Adiposity
• Biomarkers/metabolism
• Humans
• Inflammation/complications
• Insulin Resistance
• Metabolic Syndrome/etiology
• Metabolic Syndrome/metabolism
• Metabolic Syndrome/pathology
• Obesity/complications

• COPD comorbidities
• Smoking
• immunometabolism
• metabolic dysregulation
• obesity
• oxidants

• Animals
• Comorbidity
• Humans
• Metabolic Syndrome/drug therapy
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/immunology
• Metabolic Syndrome/metabolism
• Pulmonary Disease, Chronic Obstructive/drug therapy
• Pulmonary Disease, Chronic Obstructive/epidemiology
• Pulmonary Disease, Chronic Obstructive/immunology
• Pulmonary Disease, Chronic Obstructive/metabolism

• C-reactive protein
• Depression
• Glucose
• Inflammation
• Lipids
• Metabolism
• Tumor necrosis factor

• Adult
• Antidepressive Agents
• Biomarkers, Pharmacological/analysis
• Biomarkers, Pharmacological/blood
• C-Reactive Protein/analysis
• Cholesterol/metabolism
• Depression
• Depressive Disorder, Treatment-Resistant/drug therapy
• Depressive Disorder, Treatment-Resistant/metabolism
• Fatty Acids, Nonesterified
• Female
• Glucose/genetics
• Glucose/metabolism
• Humans
• Inflammation
• Infliximab/metabolism
• Infliximab/pharmacology
• Lipid Metabolism/drug effects
• Lipid Metabolism/genetics
• Male
• Middle Aged
• Triglycerides
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

• R01 MH107033 NIMH NIH HHS
• R25 MH101079 NIMH NIH HHS
• R01 MH109637 NIMH NIH HHS
• R01 MH112076 NIMH NIH HHS
• P30 CA138292 NCI NIH HHS
• R21 MH106904 NIMH NIH HHS
• R03 MH100273 NIMH NIH HHS
• UL1 TR000454 NCATS NIH HHS
• UL1 TR002378 NCATS NIH HHS
• UL1 RR025008 NCRR NIH HHS
• R01 MH087604 NIMH NIH HHS

• colon
• enteroendocrine cells
• gut microbiota
• human
• human biology
• medicine
• type 2 diabetes

• Cardiovascular disease
• Inflammation
• Metabolic syndrome
• Obesity
• PsA
• RA

• DMARDs (biologics)
• lipids
• rheumatoid arthritis

• Administration, Oral
• Adult
• Aged
• Antirheumatic Agents/administration & dosage
• Arthritis, Rheumatoid/blood
• Arthritis, Rheumatoid/diagnosis
• Arthritis, Rheumatoid/drug therapy
• Azetidines/administration & dosage
• Cholesterol, HDL/drug effects
• Cholesterol, LDL/drug effects
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage
• Lipid Metabolism/drug effects
• Male
• Middle Aged
• Purines
• Pyrazoles
• Randomized Controlled Trials as Topic
• Reference Values
• Severity of Illness Index
• Sulfonamides/administration & dosage
• Treatment Outcome

• Incyte
• Eli Lilly and Company

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are associated with inflammation. We tried to investigate the influence of tumor necrosis factor inhibitors (TNFi) and tocilizumab (TCZ) on the glucose metabolism of RA patients. RA patients in whom treatment with TNFi or TCZ was initiated from 2008 to 2015 were studied based on their medical records. We analyzed patients whose glycosylated hemoglobin (HbA1c) levels were measured both before and 3 months after the initiation of these biologic agents. The association between HbA1c reduction and the treatment was evaluated. From 971 cases treated with these biologic agents, 221 cases whose medical records of HbA1c were available, were included (TNFi, n = 154; TCZ, n = 67). Both the TNFi and TCZ groups had significantly lower HbA1c values at 1 month and 3 months after the initiation of treatment (TNFi, p<0.001; TCZ, p<0.001). Although the pretreatment HbA1c values did not differ (TNFi, 6.2%; TCZ, 6.2%; p = 0.532), the 3-month treatment HbA1c values were lower (TNFi, 6.1%; TCZ, 5.8%; p = 0.010) and the changes in HbA1c (ΔHbA1c) were greater (TNFi, 0.1%; TCZ, 0.4%; p<0.001) in the TCZ group. The reduction of HbA1c—defined by the achievement of a ΔHbA1c of ≥0.5%—was associated with baseline diagnosis of diabetes mellitus, baseline diabetes treatment, hospitalization, medical change during the observation period, and TCZ. In the multivariate logistic regression analysis, TCZ was associated with the reduction of HbA1c in comparison to TNFi (adjusted OR = 5.59, 95% CI = 2.56–12.2; p<0.001). The HbA1c levels in RA patients were significantly lower after the initiation of TNFi or TCZ. Our study suggests that TCZ decreases the HbA1c levels in RA patients to a greater extent than TNFi.

• Cardiovascular disease
• Cardiovascular risk assessment
• Mortality
• Myocardial infarction
• Rheumatoid arthritis

• K23 AR068449 NIAMS NIH HHS
• U54 MD007587 NIMHD NIH HHS
• National Institute of Arthritis and Musculoskeletal and Skin Diseases

• IGF-1 (insulin-like growth factor 1)
• IGFBP1 (IGF binding protein 1)
• TXNDC5
• diabetes
• rheumatoid arthritis

• lipid
• metabolic
• psoriasis
• triglyceride
• ustekinumab

• Carnosic acid
• Diabetic
• Inflammation suppression
• ROS-dependent p38
• Rheumatoid arthritis

• Abietanes/therapeutic use
• Animals
• Arthritis, Experimental/drug therapy
• Arthritis, Rheumatoid/drug therapy
• Cell Differentiation
• Cells, Cultured
• Disease Models, Animal
• Humans
• Immunosuppression Therapy
• Inflammation/drug therapy
• MAP Kinase Signaling System
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Osteoclasts/physiology
• Reactive Oxygen Species/metabolism
• Rosmarinus/immunology
• Rosmarinus/metabolism

During the last decade, different studies have converged to evidence the high prevalence of comorbidities in subjects with psoriasis. Although a causal relation has not been fully elucidated, genetic relation, inflammatory pathways and/or common environmental factors appear to be underlying the development of psoriasis and the metabolic comorbidities. The concept of psoriasis as a systemic disease directed the attention of the scientific community in order to investigate the extent to which therapeutic interventions influence the onset and evolution of the most prevalent comorbidities in patients with psoriasis. This study presents scientific evidence of the influence of immunobiological treatments for psoriasis available in Brazil (infliximab, adalimumab, etanercept and ustekinumab) on the main comorbidities related to psoriasis. It highlights the importance of the inflammatory burden on the clinical outcome of patients, not only on disease activity, but also on the comorbidities. In this sense, systemic treatments, whether immunobiologicals or classic, can play a critical role to effectively control the inflammatory burden in psoriatic patients.

• DMARDs (biologic)
• DMARDs (synthetic)
• Outcomes research
• Rheumatoid Arthritis

• Abatacept/therapeutic use
• Aged
• Antirheumatic Agents/therapeutic use
• Arthritis, Rheumatoid/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Drug Therapy, Combination
• Female
• Glucocorticoids/therapeutic use
• Humans
• Hydroxychloroquine/therapeutic use
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Incidence
• Longitudinal Studies
• Male
• Methotrexate/therapeutic use
• Middle Aged
• Proportional Hazards Models
• Protective Factors
• Risk Factors
• United States/epidemiology

• Anti-TNF agents
• TNF-alpha
• cardiovascular outcomes
• chronic inflammation
• rheumatic disease

• Artrite reumatoide
• Insulin resistance
• Obesidade
• Obesity
• Resistência à insulina
• Rheumatoid arthritis
• TNF-α

The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients.

A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0–6, 6–12, 12–18, and 18–24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results.

The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0–6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18–24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from –0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18–24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18–24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study.

TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.

• Ankylosing spondylitis
• Lipid profile
• Psoriatic arthritis
• Rheumatoid arthritis
• TNF-α inhibitors

The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92.

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Arthritis, Rheumatoid/complications
• Arthritis, Rheumatoid/drug therapy
• Dementia/epidemiology
• Dementia/etiology
• Dementia/prevention & control
• Disease Progression
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Incidence
• Male
• Middle Aged
• Population Surveillance/methods
• Prognosis
• Retrospective Studies
• Risk Assessment/methods
• Risk Factors
• Taiwan/epidemiology
• Time Factors
• Young Adult

Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.

• Adipokines/genetics
• Adipokines/metabolism
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Antibodies, Monoclonal/pharmacology
• Arthritis, Experimental/chemically induced
• Arthritis, Experimental/drug therapy
• Arthritis, Experimental/metabolism
• Arthritis, Experimental/pathology
• C-Reactive Protein/genetics
• C-Reactive Protein/metabolism
• Cartilage, Articular/drug effects
• Cartilage, Articular/metabolism
• Cartilage, Articular/pathology
• Cattle
• Etanercept/pharmacology
• Gene Expression
• Glucose/metabolism
• Injections, Intra-Articular
• Lipid Metabolism/drug effects
• Male
• Mice
• Mice, Inbred BALB C
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/metabolism
• Neutrophil Infiltration/drug effects
• Neutrophils/drug effects
• Neutrophils/metabolism
• Neutrophils/pathology
• Receptors, Interleukin-8A/antagonists & inhibitors
• Receptors, Interleukin-8A/genetics
• Receptors, Interleukin-8A/metabolism
• Receptors, Interleukin-8B/antagonists & inhibitors
• Receptors, Interleukin-8B/genetics
• Receptors, Interleukin-8B/metabolism
• Serum Albumin, Bovine
• Sulfonamides/pharmacology
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism

• Atherosclerosis
• Biomarkers
• Inflammation