A Brief History of IL-1 and IL-1 Ra in Rheumatology

Dayer, Jean‐Michel; Oliviero, Francesca; Punzi, Leonardo

doi:10.3389/fphar.2017.00293

Cited by 64 publications

(39 citation statements)

References 85 publications

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“…Also interesting was the association between arthralgia and increased production of IL-1ra, a soluble inhibitor of the IL-1 receptor that inhibits the function of IL-1β, a dominantly proinflammatory cytokine in inflammatory diseases affecting the joints ( 43 ). Indeed, IL-1ra production has been observed in arthralgia, probably due to a negative feedback mechanism controlling inflammation ( 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations

et al. 2018

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An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection. These profiles were then associated with symptoms, revealing important aspects of the immunopathophysiology of ZIKV infection. The levels of some cytokines/chemokines were significantly higher in acute ZIKV-infected individuals compared to healthy donors, including interferon (IFN) gamma-induced protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), IFN-γ, interleukin (IL)-9, IL-7, IL-5, and IL-1ra, including some with predominantly immunoregulatory activity. Of note, we found that higher levels of IP-10 and IL-5 in ZIKV-infected individuals were strongly associated with exanthema and headache, respectively. Also, higher levels of IL-1ra were associated with subjects with arthralgia, whereas those with fever showed lower levels of granulocyte-colony stimulating factor (G-CSF). No correlation was observed between the number of symptoms and ZIKV viral load. Interestingly, only IP-10 showed significantly decreased levels in the recovery phase. In conclusion, our results indicate that acute ZIKV infection in a larger cohort resident to an endemic area displays a modest systemic immune activation profile, involving both proinflammatory and immunoregulatory cytokines and chemokines that could participate of virus control. In addition, we showed that differential cytokine/chemokine levels are related to specific clinical symptoms, suggesting their participation in underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations

et al. 2018

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“…The pathophysiologic distinction between these conditions has therapeutic implications. Autoinflammatory diseases such as Still’s disease, Behçet’s disease, and most cases of HA20 are well treated with IL-1 blockade, which has only marginal effect in autoimmune diseases including RA ( 136 ). Autoinflammation may also underlie other chronic disorders such as atherosclerosis, as these patients benefit from anti-IL-1 therapy ( 137 , 138 ).…”

Section: A20/tnfaip3 In Autoinflammatory and Autoimmune Patientsmentioning

confidence: 99%

A20/Tumor Necrosis Factor α-Induced Protein 3 in Immune Cells Controls Development of Autoinflammation and Autoimmunity: Lessons from Mouse Models

Das¹,

Chen²,

Hendriks³

et al. 2018

Front. Immunol.

145

106

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Immune cell activation is a stringently regulated process, as exaggerated innate and adaptive immune responses can lead to autoinflammatory and autoimmune diseases. Perhaps the best-characterized molecular pathway promoting cell activation is the nuclear factor-κB (NF-κB) signaling pathway. Stimulation of this pathway leads to transcription of numerous pro-inflammatory and cell-survival genes. Several mechanisms tightly control NF-κB activity, including the key regulatory zinc finger (de)ubiquitinating enzyme A20/tumor necrosis factor α-induced protein 3 (TNFAIP3). Single nucleotide polymorphisms (SNPs) in the vicinity of the TNFAIP3 gene are associated with a spectrum of chronic systemic inflammatory diseases, indicative of its clinical relevance. Mice harboring targeted cell-specific deletions of the Tnfaip3 gene in innate immune cells such as macrophages spontaneously develop autoinflammatory disease. When immune cells involved in the adaptive immune response, such as dendritic cells or B-cells, are targeted for A20/TNFAIP3 deletion, mice develop spontaneous inflammation that resembles human autoimmune disease. Therefore, more knowledge on A20/TNFAIP3 function in cells of the immune system is beneficial in our understanding of autoinflammation and autoimmunity. Using the aforementioned mouse models, novel A20/TNFAIP3 functions have recently been described including control of necroptosis and inflammasome activity. In this review, we discuss the function of the A20/TNFAIP3 enzyme and its critical role in various innate and adaptive immune cells. Finally, we discuss the latest findings on TNFAIP3 SNPs in human autoinflammatory and autoimmune diseases and address that genotyping of TNFAIP3 SNPs may guide treatment decisions.

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“…In the last two decades, clinical practice has been revolutionized following the development and marketing of several new biologic DMARDs (bDMARDs) resulting in a dramatic improvement in the management of refractory patients [ 3 ]. These molecules can selectively target soluble mediators involved in the development and maintenance of inflammatory processes such as tumor necrosis factor-alpha (TNF-α) [ 6 ], interleukin-1 (IL-1) [ 7 ] and -6 (IL-6) [ 8 ] or surface molecules involved in T-cells activation (such as the CTLA-4—CD80/86 pathway) [ 9 ] or B cell survival signals (such surface CD20) [ 10 ]. At present, five TNF-α antagonists (TNFi) (adalimumab—ADA; etanercept—ETN; certolizumab pegol—CZP and golimumab—GOL, for subcutaneous administration; infliximab—IFX for intravenous infusion), one IL-17 inhibitor (secukinumab—SEC), one IL-12/23 inhibitor (ustekinumab—UST), one IL-6 receptor antagonist (tocilizumab—TCZ), one IL-1 inhibitor (anakinra—ANA), one T-cell co-stimulation inhibitor (abatacept—ABT), and one B-cell depleting agent (rituximab—RTX) are approved by European Medicines Agency (EMA) for treatment of patients with inflammatory arthritis.…”

Section: Introductionmentioning

confidence: 99%

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

et al. 2018

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IntroductionPost-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs’ reporting associated with biologics use in rheumatology.Materials and methodsWe developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol.ResultsDuring the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders.ConclusionsIn conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

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A Brief History of IL-1 and IL-1 Ra in Rheumatology

Cited by 64 publications

References 85 publications

Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations

Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations

A20/Tumor Necrosis Factor α-Induced Protein 3 in Immune Cells Controls Development of Autoinflammation and Autoimmunity: Lessons from Mouse Models

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

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