The Alarmin Triad—IL-25, IL-33, and TSLP—Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria

Abstract

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33’s correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria

“…There were positive correlations between IL-33 and UAS 7 and DLQI. These findings suggest that IL-33 can be seen as a diagnostic biomarker in CSU, which correlates with disease severity [ 16 ].…”

“…It is known that urticarial lesions are induced by vasoactive mediators, with the histamine released by mast cells remaining the main representative process. The genetic polymorphism of mast-cell-derived interleukins and the predisposition to develop CSU are also areas that require study and exploration [ 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…Numerous inflammatory cells (mast cells, macrophages, basophils, eosinophils) have been detected in the skin lesions of patients with CSU in association with an excessive production of inflammatory mediators (IL-4, IL-13, IL-5, IL-9, IL-10, IL-17, TNFα, IL-31, and IL-33). Systemic inflammation in CSU is supported by significantly elevated serum/plasma levels (compared to healthy individuals) of pathogenic cytokines involved in Th2 inflammation [ 5 , 14 , 16 , 17 ]. Many studies have examined the role of T cells and related cytokines in the development of CSU, but there has been limited research focusing on changes in cytokine levels during treatment.…”