A Possible Role for Soluble Il-6 Receptor in the Pathogenesis of Systemic Onset Juvenile Chronic Arthritis

Keul, Radovan; Heinrich, P.C.; Müller, Klaus; Woo, Patricia

doi:10.1006/cyto.1997.0343

Cited by 83 publications

(58 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Symptoms and signs seen in patients with systemic-onset disease are attributable to an imbalance in IL-6 homeostasis (7,19); IL-6 functions as a hepatocyte-stimulating factor that induces expression of various acute-phase proteins, including CRP, serum . The MRA treatments (3 doses each at 2, 4, and 8 mg/kg) yielded significantly better outcomes for all end points, according to the JIA core set criteria.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis

Yokota

Miyamae

Imagawa

et al. 2005

Arthritis & Rheumatism

351

199

View full text Add to dashboard Cite

Objective. To investigate the safety and efficacy of a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL-6 in children with systemiconset juvenile idiopathic arthritis (JIA) refractory to high-dose, long-term corticosteroids.Methods. An individual escalating-dose trial was conducted in 11 children with active systemic-onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4-mg/kg dose. Those without disease flares at this dose received a second 4-mg/kg dose 2 weeks later and a third 4-mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests.Results. MRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute-phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response.Conclusion. MRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute-phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL-6 and adverse events.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis

Yokota

Miyamae

Imagawa

et al. 2005

Arthritis & Rheumatism

351

199

View full text Add to dashboard Cite

show abstract

“…It plays an important role in bone biology by inducing the differentiation and activation of osteoclasts and it mediates periarticular destruction of bone and cartilage in experimental models of arthritis [87]. IL-6 levels are increased in the serum of children with Systemic onset Juvenile Arthritis in a disease activity-dependent manner [88], and blocking its receptor is emerging as an effective therapy both in SoJIA [89] as well as in adult RA [90].…”

Section: Il-6 and Its Familymentioning

confidence: 99%

Dendritic cells and cytokines in human inflammatory and autoimmune diseases

Blanco

Palucka

Pascual

et al. 2008

Cytokine & Growth Factor Reviews

456

362

View full text Add to dashboard Cite

Dendritic cells (DCs) produce cytokines and are susceptible to cytokine-mediated activation. Thus, interaction of resting immature DCs with TLR ligands, for example nucleic acids, or with microbes leads to a cascade of pro-inflammatory cytokines and skewing of T cell responses. Conversely, several cytokines are able to trigger DC activation (maturation) via autocrine, for example TNF and plasmacytoid DCs, and paracrine, for example type I IFN and myeloid DCs, pathways. By controlling DC activation, cytokines regulate immune homeostasis and the balance between tolerance and immunity. The increased production and/or bioavailability of cytokines and associated alterations in DC homeostasis have been implicated in various human inflammatory and autoimmune diseases. Targeting these cytokines with biological agents as already is the case with TNF and IL-1 represents a success of immunology and the coming years will expand the range of cytokines as therapeutic targets in autoinflammatory and autoimmune pathology.

show abstract

“…Infliximab (81 ne (43). Sin dalle prime esperienze, monocentriche prospettiche aperte, tra cui la nostra, l'inibizione del TNFα con l'anticorpo chimerico monoclonale, associato a MTX, ha portato nell'AIG attiva e refrattaria al MTX e uno o più altri DMARDs, ad una riduzione statisticamente significativa, e clinicamente sorprendente, dell'attività di malattia, ed è stata associata a un miglioramento di alcuni aspetti della qualità di vita.…”

Section: Etanercept (127 Pz)unclassified

Biological therapy with TNF-inhibitors in pediatric rheumatology. Review of the litterature and personal experience

Gerloni¹,

Pontikaki²,

Gattinara³

et al. 2011

Reumatismo

View full text Add to dashboard Cite

The therapeutic approach to JIA is sometimes very troublesome and progression to erosive polyarthritis may occur in all JIA categories. Only Methotrexate has shown efficacy and safety in a large controlled trial. Nevertheless, in many cases, drug resistance or intolerance has led to try other therapeutic options, with still debatable results. Therefore, there has been space, in the last few years, for new therapies as the TNF-inhibitors. This therapeutic approach has shown a dramatic clinical benefit in active polyarticular refractory JIA: the rate and rapidity of response have exceeded those of all other studied DMARDs. Preliminary data show that they are efficacious also for other pediatric rheumatic disease (spondyloarthropathies, autoimmune uveitis, dermatomyositis, Kawasaki syndrome and some auto- inflammatory diseases). TNF-inhibitors in JIA have demonstrated a favourable benefit-to-risk profile. However, as their use has increased worldwide, some unusual, usually not serious, adverse events have emerged. Severe infections, including TB, and deaths have been reported. Long-lasting active disease, systemic disease, concurrent and previous immunosuppressive therapies, all contribute to risk of infection and other serious AEs. Given the evidence that TNF has a primary role in the pathogenesis of JIA, particularly in joint destruction, neutralizing this cytokine early, within the window of opportunity, could halt or delay progression of joint damage and debilitating consequences of the disease. Thus, for JIA patients whose disease is not quickly controlled with MTX, TNF blockers may be considered as first-line treatment, although long-term safety data still need to be established

show abstract

A Possible Role for Soluble Il-6 Receptor in the Pathogenesis of Systemic Onset Juvenile Chronic Arthritis

Cited by 83 publications

References 0 publications

Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis

Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis

Dendritic cells and cytokines in human inflammatory and autoimmune diseases

Biological therapy with TNF-inhibitors in pediatric rheumatology. Review of the litterature and personal experience

Contact Info

Product

Resources

About