Pathogenesis and Therapy of Rheumatoid Arthritis

Williams, Richard O.

doi:10.1007/2789_2006_019

Cited by 3 publications

(2 citation statements)

References 76 publications

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“…Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is estimated to affect up to 1% of the population worldwide (Williams, 2006). Although not life‐threatening, RA is a painful and debilitating disease that progressively limits the ability of patients to carry on normal lives.…”

Section: Introductionmentioning

confidence: 99%

A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

Chen

Muramoto²,

Masaaki³

et al. 2010

British J Pharmacology

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Background and purpose: Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E2 (PGE2) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE2 EP4 receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. Experimental approach: Effects of PGE2 and a novel EP4 receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. Key results: Stimulation of the EP4 receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE2 antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen-and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. Conclusion and implications: PGE2 stimulates EP4 receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP4 receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.

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Section: Introductionmentioning

confidence: 99%

A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

Chen

Muramoto²,

Masaaki³

et al. 2010

British J Pharmacology

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“…Además se retrasó la aparición de erosiones radiológicas y la disminución del espacio articular en AR. 2,3,4,5 Está información se ha obtenido en especial en poblaciones anglosajonas y asiáticas, 6 con un contexto diferente al nuestro; hemos querido realizar un estudio en nuestra población para describir los efectos del tratamiento con infliximab en los pacientes con AR que reciben diferentes medicamentos modificadores de la enfermedad incluyendo metotrexate. Por tanto, el objetivo de este trabajo fue evaluar nuestra experiencia clínica con el uso de infliximab en 73 pacientes con AR que recibían distintos fármacos antirreumáticos incluyendo metotrexate.…”

Section: Introductionunclassified

Desenlaces clínicos en artritis reumatoidea tratada con infliximab: Hospital de San José, 2007-2008

Perdomo¹,

Nieto²,

Mejía³

et al. 2009

Repert. Med. Cir.

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Objetivo: describir los resultados clínicos obtenidos en los pacientes con artritis reumatoidea que recibieron infliximab durante el período enero de 2007 a octubre de 2008. Pacientes y métodos: se revisaron 240 historias clínicas de enfermos con AR atendidos en el lapso correspondiente, de las cuales 73 tenían información disponible que cumpliera los criterios de inclusión y exclusión. Se analizaron las características clínicas y sociodemográficas, el comportamiento de la respuesta terapéutica si la hubo y el tiempo de aparición, el uso de medicamentos coadyuvantes y el desarrollo de eventos adversos. Resultados: se describieron 73 pacientes, de los cuales el 89,04% fueron mujeres con edad promedio de 49.7 años y evolución de la AR de 12.0 (± 8.8) años, quienes recibieron 3 mg/k de infliximab con un número promedio de dosis de 9.1. Se obtuvo respuesta terapéutica en 52,05% a las 24.15 (±19.5) semanas de tratamiento. En contraste, los pacientes restantes que aun no tenían mejoría y continuaban con el tratamiento, llevaban con el medicamento un promedio de 26.65 (±22.5) semanas. La terapia fue suspendida en 29 pacientes: 11 (15,06%) de manera temporal y 18 (24,65%) permanente. Conclusiones: el infliximab redujo la actividad inflamatoria en más de la mitad de los enfermos del presente estudio con una baja frecuencia de efectos adversos. Dicha respuesta se documentó con el control en las articulaciones dolorosas e inflamadas. No hubo relación positiva con los marcadores inflamatorios, aclarando el bajo reporte de los mismos en las historias clínicas revisadas. Abreviaturas: AR, artritis reumatoidea; FNT-a, factor de necrosis tumoral; CAR, Colegio Americano de Reumatología.

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Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

Pretorius

Akeredolu

Soma

et al. 2016

Exp Biol Med (Maywood)

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We review the evidence that infectious agents, including those that become dormant within the host, have a major role to play in much of the etiology of rheumatoid arthritis and the inflammation that is its hallmark. This occurs in particular because they can produce cross-reactive (auto-)antigens, as well as potent inflammagens such as lipopolysaccharide that can themselves catalyze further inflammagenesis, including via β-amyloid formation. A series of observables coexist in many chronic, inflammatory diseases as well as rheumatoid arthritis. They include iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. Iron dysregulation may be responsible for the periodic regrowth and resuscitation of the dormant bacteria, with concomitant inflammagen production. The present systems biology analysis benefits from the philosophical idea of “coherence,” that reflects the principle that if a series of ostensibly unrelated findings are brought together into a self-consistent narrative, that narrative is thereby strengthened. As such, we provide a coherent and testable narrative for the major involvement of (often dormant) bacteria in rheumatoid arthritis.Impact statementRheumatoid arthritis (RA) is accompanied by long-term inflammation that is mediated by cytokines and cross-reactive (auto-)antigens. Here we suggest one explanation is the presence of a (dormant) microbiome in RA that sheds the highly potent inflammagen, lipopolysaccharide lipopolysaccharides (LPS) to catalyze inflammagenesis, including via β-amyloid formation. We discuss various co-existing features in RA, including iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. We review literature and provide coherent evidence that an aberrant blood microbiome in RA has a major involvement in the development, progression, and therefore over-all etiology of the disease.

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Pathogenesis and Therapy of Rheumatoid Arthritis

Cited by 3 publications

References 76 publications

A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

Desenlaces clínicos en artritis reumatoidea tratada con infliximab: Hospital de San José, 2007-2008

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

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Pathogenesis and Therapy of Rheumatoid Arthritis

Cited by 3 publications

References 76 publications

A novel antagonist of the prostaglandin E2 EP4 receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

A novel antagonist of the prostaglandin E2 EP4 receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

Desenlaces clínicos en artritis reumatoidea tratada con infliximab: Hospital de San José, 2007-2008

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

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A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models

A novel antagonist of the prostaglandin E₂ EP₄ receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models