Original Research
Immunology / Allergic Diseases

Association Between IL-31 Serum Levels and Other Predisposing Factors with Allergic Diseases in HRPZ II and HUSM, Kelantan, Malaysia

Last reviewed: March 2026

Introduction

Allergic diseases—including atopic dermatitis (eczema), allergic rhinitis (hay fever), and atopic asthma—represent a major global health burden, affecting hundreds of millions of people worldwide. These conditions share a common immunological basis involving immunoglobulin E (IgE)-mediated hypersensitivity and T-helper type 2 (Th2) immune responses. In Malaysia, allergic diseases are increasingly prevalent, particularly among the younger population, with house dust mites, cat fur, and fungal allergens identified as key sensitising agents.

Interleukin-31 (IL-31) is a cytokine that was identified in the early 2000s and has since attracted considerable research interest for its role in allergic inflammation and particularly in pruritus (itching), one of the most distressing symptoms of allergic skin diseases. IL-31 is primarily produced by activated CD4+ T cells, particularly those of the Th2 subtype, and signals through a heterodimeric receptor complex expressed on various cell types including keratinocytes, dorsal root ganglia neurons, and immune cells. The ability of IL-31 to induce itching sensations through direct neuronal stimulation has made it a target for therapeutic development, with anti-IL-31 receptor antibodies now in clinical trials for atopic dermatitis.

This study investigated the association between serum IL-31 levels and allergic diseases in a Malaysian population, conducted across two major healthcare facilities in Kelantan: Hospital Raja Perempuan Zainab II (HRPZ II), the state general hospital, and Hospital Universiti Sains Malaysia (HUSM), the teaching hospital of Universiti Sains Malaysia’s Health Campus.

Methodology

The study employed a comparative cross-sectional design. Cases were patients diagnosed with allergic diseases—including atopic dermatitis attending the dermatology clinic, allergic rhinitis attending the ENT (ear, nose, and throat) clinic, and atopic asthma attending chest and paediatric clinics—at HUSM and HRPZ II in Kelantan, Malaysia. Diagnosis was confirmed through clinical assessment by specialist physicians according to established diagnostic criteria (including the ARIA classification for allergic rhinitis).

Control subjects were recruited from healthy individuals in the community served by HUSM. Blood samples were collected from all participants, centrifuged to obtain serum, and analysed for IL-31 levels using enzyme-linked immunosorbent assay (ELISA) kits. Additional predisposing factors and clinical parameters were recorded, including family history of atopic diseases, smoking status, disease severity assessments, and the presence or absence of pruritus.

Statistical analysis employed independent t-tests and Mann-Whitney U tests to compare IL-31 levels between groups, with significance set at p < 0.05. The study included a total of 210 allergic patients, with the majority being female (64.8%) and non-smokers (82.5%).

Results

The analysis of IL-31 serum levels yielded complex results that reflected the emerging and sometimes inconsistent literature on this cytokine’s role in allergic diseases. IL-31 serum levels were generally higher in allergic patients compared to healthy controls, but the magnitude and statistical significance of these differences varied across disease subgroups.

For allergic rhinitis specifically, the mean serum IL-31 level was higher in patients than in normal controls; however, this difference did not reach statistical significance. Similarly, no significant difference in IL-31 levels was observed between patients with different severities of allergic rhinitis. These findings contributed to a nuanced understanding of IL-31’s role—while this cytokine is clearly involved in allergic inflammation at the tissue level, its serum levels may not consistently reflect local tissue concentrations or disease activity.

Analysis of the relationship between IL-31 and pruritus showed that while there was a trend towards higher levels in patients reporting pruritus, the high variability in individual measurements limited the statistical power to detect significant differences. The large standard deviations observed in IL-31 measurements across groups suggested substantial inter-individual variation in cytokine production and clearance.

IL-31 in the Context of Allergic Disease Pathophysiology

IL-31 belongs to the gp130/IL-6 cytokine family and exerts its biological effects through the IL-31 receptor A (IL-31RA) and oncostatin M receptor beta (OSMR-β). In the skin, IL-31 promotes inflammation by inducing chemokine production from keratinocytes, recruiting inflammatory cells, and directly stimulating sensory neurons to produce itch. Patients with atopic dermatitis have been shown to have elevated IL-31 mRNA expression in skin lesions and, in many studies, elevated serum levels that correlate with disease severity.

The clinical significance of IL-31 has been validated by the therapeutic success of nemolizumab, a monoclonal antibody targeting IL-31RA, which has demonstrated efficacy in reducing pruritus and disease severity in atopic dermatitis clinical trials. This therapeutic evidence supports the biological importance of the IL-31 signalling pathway even in cases where serum level measurements may not fully capture its pathological role.

In the Malaysian context, the study of allergic disease biomarkers is particularly relevant given the high prevalence of atopic conditions, the tropical climate that supports year-round allergen exposure, and the multiethnic population that may harbour genetic variations influencing immune responses. Research from HUSM and HRPZ II has contributed importantly to understanding allergic disease epidemiology and immunology in the Kelantan population specifically and in Malaysia more broadly.

Public Health Implications and Significance

While the serum IL-31 findings were not uniformly statistically significant, the study contributes to the growing body of evidence exploring immune biomarkers in allergic diseases within Southeast Asian populations. The research highlights the potential and challenges of using serum cytokine levels as biomarkers for allergic disease diagnosis or monitoring, and suggests that tissue-level measurements or stimulated cytokine production assays may be needed to complement serum measurements.

For Malaysian clinical practice, these findings support the continued investigation of immune biomarkers that could improve allergic disease diagnosis, severity assessment, and therapeutic monitoring. The identification of predisposing factors associated with allergic diseases in the Kelantan population contributes to a more complete understanding of allergic disease risk in Malaysia and may inform targeted prevention strategies.

Limitations

The cross-sectional design limits the ability to establish temporal relationships between IL-31 levels and disease outcomes. Serum IL-31 levels represent a single time-point measurement and may not capture the dynamic nature of cytokine production during allergic inflammation. The high variability in IL-31 measurements suggests that larger sample sizes may be needed to detect clinically meaningful differences. The hospital-based recruitment of cases may introduce selection bias compared to community-based sampling. The study was conducted in Kelantan, and findings may not be fully generalisable to other Malaysian states with different demographic and environmental characteristics.

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