IL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis

Abstract

BackgroundSevere pruritus is the primary symptom in atopic dermatitis (AD). Recently, the novel cytokine IL-31 has been implicated in the itching associated with AD.ObjectiveWe performed this study to determine whether IL-31 serum levels are elevated in AD patients and to better characterize the relationship between serum IL-31 level and other established laboratory parameters.MethodsWe recruited 55 AD patients, 34 with allergic type AD and 21 with non-allergic type AD, and 38 healthy, non-atopic controls. We checked the laboratory values, severity score, and serum IL-31 levels in all patients and controls, and IL-31 mRNA levels in lesion skin were measured in 13 subjects with AD and in four controls.ResultsAD patients displayed significantly higher levels of serum IL-31 that were associated with serum IgE, disease severity, and subjective itch intensity. In AD patients, IL-31 mRNA levels from the lesional skin samples also correlated with serum IL-31 level.ConclusionIL-31 is likely one of the many mediators inducing inflammation and pruritus in AD. Although our limited sample size prevents us from making any definitive conclusions, our data demonstrate a strong correlation between IL-31 mRNA level and serum IL-31 protein level, which has never been reported before. Moreover, we found correlations between serum IL-31 level and serum IgE, eosinophil cationic protein, disease severity, and subject itch intensity in certain degrees in AD patients.

Biomarkers for atopic dermatitis

“…45 And a recent cross-sectional study of Nygaard et al that included 163 adults and children with AD, was unable to confirm the correlation between serum IL-31 and disease severity. 46 Kim et al found that IL-31 mRNA expression is higher in biopsies from AD patients with high pruritus scores compared to patients with low pruritus scores, 47 suggesting that measurement of IL-31 in skin may be a more relevant measure for itch. Although IL-31 expression patterns in skin biopsies may also be extremely helpful in stratification, skin biopsies are invasive, require trained personnel and specialized labs.…”

Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network

“…In this study, we report on our studies to clarify further the molecular and functional consequences of IL-31 signaling in keratinocytes. Primary normal keratinocytes express very low levels of IL-31RA, which can be induced by IFN-g (33)(34)(35)(36)41). However, such treatment has additional consequences, including cell cycle arrest, making it difficult to distinguish between IFN-g-and IL-31-specific effects.…”

“…IL-31 belongs to the IL-6 family of proinflammatory cytokines and signals through heterodimeric receptors composed of the oncostatin M receptor and the IL-31-specific receptor IL-31RA (30)(31)(32). IL-31 expression is increased in lesions and serum of patients with AD and correlates with disease severity (30,(33)(34)(35)(36). Furthermore, distinct haplotypes of the IL31 gene are associated with AD (27,37,38).…”

TRP Channels and Pruritus

“…As in the case of IL-13, transgenic overexpression of IL-31 also induced severe pruritus and dermatitis in mice [144]. Further supporting its role, increased expression of IL-31 was found both in an atopic mouse model [145] and in AD patients [146,147] in good correlation with the scratching behavior in mice [148] and the symptom severity in humans [149,150]. The exact pruritogenic mechanism of action of IL-31 is still unclear although IL-31 receptors were detected on a fraction of small diameter sensory neurons [151] as well as on normal human epidermal keratinocytes (NHEKs) [152].…”