The interleukin-1 family cytokines in psoriasis: pathogenetic role and therapeutic perspectives

ABSTRACT

Introduction: IL-1 family cytokines play an important role in the innate immune system and their uncontrolled activation and expression can initiate a pathologic inflammatory response. Their role in psoriasis, pustular psoriasis, and psoriatic arthritis has been studied, and they offer potential interest as therapeutic targets.

Areas covered: This review focuses on the role that interleukin (IL)-1 family cytokines play in psoriasis pathogenesis, with a special focus on pustular psoriasis, and how these cytokines can be used as therapeutic targets. Using PubMed, we review the literature for articles related to IL-1 family cytokines and psoriasis, focusing on pustular psoriasis, and including pathogenesis, genetics and therapeutic targets.

Expert opinion: IL-1 and IL-36 cytokines act as critical drivers of the autoinflammatory responses involved in pustular psoriasis. Studies on the specific role of each IL-1 cytokine are needed, as well as of their regulatory pathways. Targeting of IL-1 family cytokines has been used in pustular psoriasis, with IL-1 and IL-36 R blockade showing promising results.

KEYWORDS:

• IL-1
• IL-36
• IL-18
• IL-37
• IL-38
• IL-36R
• psoriasis
• pustular psoriasis
• imsidolimab
• spesolimab
• pathogenesis

Article highlights

• IL-1 family cytokines act as critical regulators of the innate immune system, maintaining endogenous homeostasis. Uncontrolled activation and expression of these cytokines results in pathologic inflammatory responses, including pustular psoriasis.

• IL-1 and IL-36 cytokines act as critical drivers of the autoinflammatory responses involved in pustular psoriasis. They lead to the release of chemokines that promote activation of neutrophils, macrophages, dendritic cells, and T cells in psoriatic skin lesions.

• Several autoinflammatory conditions caused by specific monogenic mutations in genes regulating the IL-1 family have been described in recent years. Genes involved in pustular psoriasis include IL-1RA (causing DIRA), IL-36RA (causing DITRA), CARD14, AP1S3, TNIP1 and SERPINA3 genes.

• The IL-1β monoclonal antibody Canakinumab has been used in GPP and PPP, with anecdotal evidence of successful outcomes. Anti-IL36R antibodies spesolimab and imsidolimab are currently being tested in Phase II and III studies with GPP patients, with promising results.

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Financial disclosure

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Declaration of interest

H. Iznardo none; L. Puig has perceived consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB.

Acknowledgments

None

Declaration of interest

L. Puig has perceived consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.