Interleukin-18: a biomarker with therapeutic potential in adult-onset Still’s disease

ABSTRACT

Introduction

Adult-onset Still’s disease (AOSD) is an autoinflammatory disease driven by the innate immune response. Given the ambiguity in clinical presentation and lack of specific diagnostic biomarkers, AOSD diagnosis is usually delayed in the early stage. Because AOSD is a rare disease with clinical heterogeneity, there is no consensus on its treatment currently. This review summarizes the current research evidence regarding the pathogenic role and the diagnostic or therapeutic potential of interleukin (IL)-18 in AOSD.

Areas covered

We searched the MEDLINE database using the PubMed interface and reviewed English-language literature from 1971 to 2022. This review focusing on IL-18 discusses its pathogenic role and clinical implications in AOSD.

Expert opinion

NLRP3-inflammasome activation with IL-18 overproduction plays a pathogenic role in AOSD. IL-18 is closely linked to the clinical manifestations and disease activity of AOSD and may be a diagnostic biomarker. Given its pathogenic role in AOSD, IL-18 could become a potential therapeutic target. IL-18 binding protein (IL-18BP) negatively regulates the biological activity of IL-18 by inhibiting IL-18 signaling, and a clinical trial revealed that IL-18BP (Tadekinig alfa) treatment was well-tolerated and effective for AOSD. Recently, monoclonal antibodies against IL-18 have been under evaluation in a phase 1b trial.

KEYWORDS:

• Interleukin-18
• biomarker
• therapeutics
• autoinflammatory diseases
• adult-onset still’s disease (AOSD)

Article highlights

• NLRP3-inflammasome activation with IL-18 overproduction plays a pathogenic role in AOSD.

• IL-18 is closely linked to clinical manifestations and may be a diagnostic biomarker and activity indicator.

• IL-18 may be used to differentiate the systemic from the articular subtype of AOSD disease courses.

• IL-18 binding protein has therapeutic potential for AOSD by inhibiting IL-18 signaling.

• Anti-IL-18 monoclonal antibodies and strategies to suppress IL-18 production, including miR-223, mROS inhibitors, or calcium channel blockers, may have future therapeutic potential for AOSD.

Declaration of interest

The authors have no 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 on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors made substantive intellectual contributions to this review and approved the final manuscript to be published. P-K Chen, S-J Wey, and D-Y Chen performed the literature search and appraised the selected articles. P-K Chen and D-Y Chen drafted the manuscript. S-J Wey and D-Y Chen revised the final manuscript.

Additional information

Funding

This paper was not funded.