Tumor Necrosis Factor Blockade Differentially Affects Innate Inflammatory and Th17 Cytokines in Rheumatoid Arthritis

Zivojinović, S; Pejnović, Nada; Sefik-Bukilica, M.; Kovacevic, Ljiljana; Soldatović, Ivan; Damjanov, Nemanja

doi:10.3899/jrheum.110697

Cited by 27 publications

(14 citation statements)

References 15 publications

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“…Other groups have reported that ETN treatment reduces serum IL-6 [12][13][14], but there has been no direct comparison of these two TNF inhibitors in terms of cytokine profiles and clinical responses. We performed longitudinal measurements of serum proinflammatory cytokines in biologics-naïve RA patients, and analyzed the relationship between cytokine profile and clinical effectiveness.…”

Section: Introductionmentioning

confidence: 95%

Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

et al. 2015

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Section: Introductionmentioning

confidence: 95%

Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

et al. 2015

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“…At 24 weeks of treatment, serum samples of etanercept (also known as Enbrel, TNF binding protein) plus methotrexate responders had decreased IL-6 whereas increased IL-32 and IL-21. However, there were no differences in cytokine levels in non-responders (18). Pro-inflammatory cytokines contribute to persistent in chronic inflammation of RA and Etanercept therapy regulates level of serum cytokines.…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 84%

Interleukin-32 in Inflammatory Autoimmune Diseases

Kim

2014

Immune Netw

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Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-α (TNFα) and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.

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“…Both etanercept and adalimumab have been approved by the U.S. Food and Drug Administration (FDA) for human use to prevent inflammatory processes in RA. In RA patients treated with TNF-α inhibitors, serum Th17-related cytokines decreased significantly in parallel with clinical remission in the responders, whereas increased percentage of Th17 cell and elevating related cytokine levels were found in non-responders [6, 7]. However, mechanisms of how these TNF-α inhibitors suppress cytokine production, especially the immunomodulatory effects on Th17 cells, are yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

The immunomodulatory effects of TNF-α inhibitors on human Th17 cells via RORγt histone acetylation

Lin

et al. 2016

Oncotarget

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The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification. Human CD4+ T cells from healthy subjects and patients with RA were pretreated with TNF-α inhibitors and then being polarized into IL-17-producing cells. The Th17-related cytokine levels in the culture supernatants were determined with an enzyme-linked immunosorbent assay. Intracellular signalling was investigated by western blot, real-time RT-PCR, and chromatin immunoprecipitation. Th17-polarized cells from patients with RA produced more IL-17A, IL-17F and IL-22 than those from healthy subjects. Etanercept and adalimumab suppressed IL-17A, IL-17F and IL-22 levels in Th17-polarized cells from healthy subjects and patients with RA. Western blot analysis revealed that etanercept and adalimumab decreased mitogen-activated protein kinase-phospho-p38, nuclear factor-κB-phospho-p65, phospho-STAT3 and RORγt levels. Etanercept and adalimumab decreased histone (H)3 and H4 acetylation in the RORγt gene promotor region by decreasing the recruitment of the acetyltransferases p300, CBP and PCAF. The present study broadens our knowledge of the mechanisms underlying the immunomodulatory effects of TNF-α inhibitors in rheumatoid arthritis treatment.

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Tumor Necrosis Factor Blockade Differentially Affects Innate Inflammatory and Th17 Cytokines in Rheumatoid Arthritis

Cited by 27 publications

References 15 publications

Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis

Interleukin-32 in Inflammatory Autoimmune Diseases

The immunomodulatory effects of TNF-α inhibitors on human Th17 cells via RORγt histone acetylation

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