Update on the management of systemic juvenile idiopathic arthritis and role of IL-1 and IL-6 inhibition

Grevich, Sriharsha; Shenoi, Susan

doi:10.2147/ahmt.s109495

Cited by 50 publications

(52 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Matrix metalloproteinase-8 (MMP-8), a collagencleaving enzyme released by neutrophils, is a key component in the degradation of extracellular matrix in conditions such as periodontitis, cardiovascular disease, rheumatoid arthritis, and cancer [1][2][3]. Interleukin-6 (IL-6), a proinflammatory cytokine secreted by macrophages and T cells in tissue damage and inflammation, is an important mediator in host response to infections and various autoimmune diseases [4][5][6]. During pregnancy, elevated levels of cervical and amniotic fluid (AF) MMP-8 and IL-6 have been linked to the process of cervical ripening and the impending onset of labor [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

et al. 2018

View full text Add to dashboard Cite

Introduction: Intra-amniotic inflammation is defined by elevated inflammatory biomarkers in the amniotic fluid (AF), either due to microbial invasion of the amniotic cavity (MIAC) or sterile inflammation. Amniocentesis being an invasive procedure, we wanted to investigate whether elevated matrix metalloproteinase-8 (MMP-8) or interleukin-6 (IL-6) concentrations could be detected from cervical fluid samples. Materials and Methods: This prospective study included 67 women with singleton nondiabetic pregnancies with or without preterm premature rupture of membranes (PPROM) between 22 +0 and 37 +0 weeks of gestation. Simultaneous AF and cervical samples were obtained. Results: In women without PPROM, cervical MMP-8 concentrations correlated with AF MMP-8 concentrations (r S = 0.466, p = 0.002), but cervical IL-6 did not correlate with AF IL-6 (r S = 0.277, p = 0.076). In PPROM cases no correlations were found. Women with MIAC had higher concentrations of AF MMP-8 and AF IL-6 compared to women without MIAC regardless of membrane status. However, only women without PPROM had higher concentrations of cervical MMP-8 in proven MIAC. Conclusion: In women without PPROM, cervical MMP-8 concentration reflects the magnitude of AF MMP-8, thus potentially guiding the selection of patients benefitting from amniocentesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Tocilizumab is a fully humanized monoclonal antibody against both soluble and membrane-bound IL-6 receptors. It is currently FDA approved for the treatment of SJIA and RA, and it has profoundly improved disease outcomes [166]. A study by Tappeiner et al has reported that two out of three patients with JIA-related uveitis responded to tocilizumab that was refractory to anti-TNF-α therapy [167].…”

Section: Tocilizumabmentioning

confidence: 99%

Biological Therapies that Target Inflammatory Cytokines to Treat Uveitis

Reddy¹,

Muhammad²,

Lee³

2019

Advances in the Diagnosis and Management of Uveitis

View full text Add to dashboard Cite

Uveitis is a leading cause of blindness that presents a considerable challenge given that our understanding of the mechanisms of disease is still evolving. Both innate and adaptive immunity play a role in disease and mediators of these responses can serve as therapeutic targets. TNF-α and IL-1β inflammatory cytokines are central mediators of immunity and are involved in the dysregulated inflammatory response during uveitis. Because toxicity limits the use of steroids and other steroid-sparing agents, biologics that target a specific cell type or pathway are being explored for the treatment of autoimmune uveitis. This chapter begins with a broad overview of the aberrant immune response resulting in uveitis, and highlights key mediators such as TNF-α, IL-1β, IL-6, and IL-17 and their potential use as therapeutic targets. Most biological agents discussed in this review have not been FDAapproved for uveitis. However, favorable outcomes in early trials and FDA approval of these drugs for the treatment of other autoimmune diseases associated with uveitis support the potential for these biological agents in the management of uveitis. This review aims to provide an updated report on the efficacy of biologics that target TNF-α, IL-1β, IL-6, and IL-17 for the treatment of autoimmune uveitis.

show abstract

“…MAS may occur spontaneously, as a complication of active underlying disease, or may be triggered by an infection, a change in drug therapy, or toxic effect of a medication. The acute and dramatic onset of this entity often mimics a flare of the underlying disease or a severe sepsis [1]. Adenoviruses are emerging as an important cause of respiratory tract infections and can lead to significant morbidity in the immunocompromised.…”

Section: Introductionmentioning

confidence: 99%

Experience with Cidofovir as an adjunctive therapy in a patient of adenovirus-induced macrophage activation syndrome in systemic arthritis

et al. 2020

View full text Add to dashboard Cite

A 5-year-old female child, with known systemic juvenile idiopathic arthritis diagnosed at 18 months of age (on low dose Prednisolone + Methotrexate + Leflunomide + Tocilizumab), presented with fever for 1 day, vomiting, drowsiness followed by seizures. On admission to PICU, she was drowsy, tachycardic, tachypneic, with rashes, and hepatosplenomegaly. Lab findings showed thrombocytopenia, leucopenia, low ESR, normal CRP, elevated liver enzymes, high ferritin, LDH, and triglycerides suggestive of macrophage activation syndrome (MAS). Chest X-ray showed left basal pneumonia and DNA PCR of throat swab revealed adenovirus. She was diagnosed as adenovirus-triggered MAS and was initiated on pulse methylprednisolone (6 mg/kg). Because of suboptimal response after 2 doses, manifested by increasing drowsiness, further fall in platelets and rising ferritin, methylprednisolone dosage was increased to 30 mg/kg/day with the addition of oral cyclosporine (4 mg/kg/day). In view of worsening of the chest X-ray and increasing oxygen requirement, Cidofovir infusion (1 mg/kg thrice weekly) was also started simultaneously considering increased activity of the adenoviral infection concurrent to immunosuppression. Within 48 h, the child showed signs of recovery with improved consciousness, lower oxygen requirements, and improving lab parameters. She was discharged after 3 weeks of IV Cidofovir, on oral prednisolone and cyclosporine. To the best of our knowledge, this is the first reported use of Cidofovir in adenovirus-induced MAS.

show abstract

Update on the management of systemic juvenile idiopathic arthritis and role of IL-1 and IL-6 inhibition

Cited by 50 publications

References 78 publications

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

Biological Therapies that Target Inflammatory Cytokines to Treat Uveitis

Experience with Cidofovir as an adjunctive therapy in a patient of adenovirus-induced macrophage activation syndrome in systemic arthritis

Contact Info

Product

Resources

About