RESUMO
BACKGROUND: Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. OBJECTIVES: In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. METHODS: To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. RESULTS: Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. CONCLUSION: As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.
Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Traumatismos Cardíacos , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Terapia Biológica , Biomarcadores , Etanercepte/uso terapêutico , Proteína 3 Ligante de Ácido Graxo , Traumatismos Cardíacos/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfaRESUMO
Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Inibidores de Janus Quinases/efeitos adversos , Janus Quinases/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Tromboembolia/patologia , Animais , Artrite Reumatoide/enzimologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Neoplasias/enzimologia , Transdução de Sinais , Tromboembolia/induzido quimicamenteRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.
Assuntos
Dietoterapia , Suplementos Nutricionais , Lúpus Eritematoso Sistêmico/imunologia , Animais , Dieta , Ácidos Graxos Insaturados/uso terapêutico , Humanos , Imunomodulação , Lúpus Eritematoso Sistêmico/dietoterapia , Minerais/uso terapêutico , Polifenóis/uso terapêuticoRESUMO
BACKGROUND: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. METHODS: Different electronic databases were searched in a non-systematic way to find out the literature of interest. RESULTS: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still's diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. CONCLUSION: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.
Assuntos
Autoimunidade , Ferritinas/sangue , Distúrbios do Metabolismo do Ferro/sangue , Ferro/sangue , Síndrome Antifosfolipídica/sangue , Biomarcadores/sangue , Humanos , Síndrome de Ativação Macrofágica/sangue , Sepse/sangue , Doença de Still de Início Tardio/sangueRESUMO
Treatment with anti-TNF-α (tumor necrosis factor), one of the pivotal cytokines, was introduced to clinical practice at the end of last century and revolutionized the treatment of rheumatoid arthritis (RA) as well as many other inflammatory conditions. Such a treatment may however bring many safety issues regarding infections, tuberculosis, as well as cardiovascular diseases, including heart failure. Given the central role of proinflammatory cytokines in RA, atherosclerosis, and congestive heart failure (CHF), such a treatment might result in better control of the RA process on the one side and improvement of heart function on the other. Unfortunately, at the beginning of this century two randomized controlled trials failed to show any benefit of anti-TNF treatment in patients with heart failure (HF), suggesting direct negative impact of the treatment on morbidity and mortality in HF patients. As a result the anti-TNF treatment is contraindicated in all patients with heart failure and a substantial portion of patients with RA and impaired heart function are not able to benefit from the treatment. The role of TNF in CHF and RA differs substantially with regard to the source and pathophysiological function of the cytokine in both conditions, therefore negative data from CHF studies should be interpreted with caution. At least some of RA patients with heart failure may benefit from anti-TNF treatment, as it results not only in the reduction of inflammation but also contributes significantly to the improvement of cardiac function. The paper addresses the epidemiological data of safety of anti-TNF treatment in RA patients with the special emphasis to basic pathophysiological mechanisms via which TNF may act differently in both diseases.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Treatment targeting TNF revolutionized management for rheumatoid arthritis patients offering attainment of clinical remission, preventing patients from disability and improving their quality of life. Anti-cytokine therapy, however may in some circumstance contribute to development of serious adverse effects, including congestive heart failure. The heart failure in patients treated with anti-TNF agents seems to be paradoxical as TNF plays an important pathogenetic role in both conditions. In congestive heart failure, TNF may act as a regulatory factor and may stabilize the heart function, so TNF blockade may result in progression of the heart failure. In this paper, the pathogenetic role of TNF has been discussed with the special emphasis to the role of cytokine in conditions of heart failure and systemic inflammation.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Sistemas de Liberação de Medicamentos/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Inibidores do Fator de Necrose Tumoral , Artrite Reumatoide/psicologia , Humanos , Qualidade de VidaRESUMO
OBJECTIVE: To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA). METHODS: We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year. RESULTS: Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study. CONCLUSION: In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.