The dark side of the moon: the immune-mediated adverse events of IL-17A/IL-17R inhibition

Messina, Francesco; Piaserico, Stefano

doi:10.1080/09546634.2022.2062281

Cited by 18 publications

(11 citation statements)

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“…The production of inflammatory cytokines characteristic of psoriasis skin lesions. These cytokines can induce the differentiation of Th17 cells and keratinocyte hyperproliferation (Messina & Piaserico, 2022). Consistent with our previous research results, the mRNA ( p < 0.0001; Figure 4a–d) expression of inflammatory cytokines in skin lesions and also the IL‐6, TNF‐α, IL‐23 and IL‐17A proteins in supernatants were increased in vehicle mice, while LQ reduced the production of those cytokines ( p < 0.001; Figure 4e–h).…”

Section: Resultsmentioning

confidence: 99%

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Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF‐κB and AP‐1 pathway

Guo,

Wang,

et al. 2023

Phytotherapy Research

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Psoriasis is a common immune‐mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF‐α with or without liquiritin, harvested for analysis by western blots and RT‐qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ‐L and LQ‐H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT‐qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod‐induced psoriasis‐like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF‐α‐induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod‐induced mice, the activation of NF‐κB and AP‐1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF‐κB and AP‐1 signal pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Lq Decreases the Production Of Inflammatory Cytokines In Imq...mentioning

confidence: 99%

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF‐κB and AP‐1 pathway

Guo,

Wang,

et al. 2023

Phytotherapy Research

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“…Activated keratinocytes can induce chemotaxis of neutrophils (IL-8), thus contributing to pustular psoriasis ( 24 ). Genetic factors may also be related to this adverse reaction, although definitive evidence is lacking ( 25 ). In summary, disrupting a particular cytokine network may lead to new autoimmune inflammatory phenomenon in patients treated with biologics, meriting further investigation to elucidate the causal relationship.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical reaction to IL-17A inhibitor: a case report and literature review

Ren,

Deng,

Guo

et al. 2024

Front. Med.

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ObjectiveA case of pustular psoriasis after treatment with secukinumab in a patient with plaque psoriasis is reported, which is the first case in China. To summarize the clinical characteristics of patients who developed the rare paradoxical reaction and treatment options received IL-17A antagonist therapy, we conducted a further literature review.MethodsData were analyzed from a patient with plaque psoriasis who developed pustular psoriasis after treatment with secukinumab. A comprehensive review of relevant domestic and international literature was conducted, focusing on cases that met our inclusion criteria for analysis and synthesis.ResultsAnti IL-17A therapy may lead to type conversion, with reported cases more prevalent in women and varying in onset time, predominantly involving palmoplantar pustulosis.ConclusionGiven the increasing use of IL-17A antagonists in psoriasis treatment, it is crucial to monitor for rare adverse reactions, including the paradoxical induction of pustular psoriasis.

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“…Secukinumab, an anti-interleukin (IL)-17A IgG1-κ monoclonal antibody, is approved for use in psoriasis, psoriatic arthritis, and ankylosing spondylitis. However, rare side effects of IL-17 pathway inhibition such as paradoxical psoriasis and atopic-like eczema associated with dermatological manifestations have been already described (10). Rituximab, a genetically engineered chimeric murine/ human monoclonal antibody that targets CD20, a B-cell specific surface antigen, is recommended for the treatment of hematologic malignancies, systemic lupus erythematosus, rheumatoid arthritis, microscopic polyangiitis, granulomatosis with polyangiitis and pemphigus vulgaris; however, paradoxical phenomena such as its induction of vasculitis and worsening of pemphigus vulgaris have also been reported (11,12).…”

Section: Letters To Editor Rheumatologymentioning

confidence: 99%