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 Table of Contents  
Year : 2019  |  Volume : 39  |  Issue : 2  |  Page : 66-70

Serum levels of interleukin-38 in sufferers with atopic eczema

1 Dermatology, Venereology and Andrology and Departments, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Clinical Pathology, Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission19-Jan-2019
Date of Acceptance04-Apr-2019
Date of Web Publication03-Jul-2019

Correspondence Address:
Fathia M Khattab
Assistant Professor of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, 44511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejdv.ejdv_2_18

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Background The relation between interleukin-38 (IL-38) and atopy is not precisely regarded yet. The current study has a look at set to assess the serum level of IL-38 in atopy patients and controls in order to illustrate the disease association and correlation with severity.
Objective The aim of this study was to quantify serum IL-38 titers in atopic dermatitis patients and to observe relationships with disease severity‏‏.
Patients and method s Twenty-six atopic cases along with 26 healthy controls were attributed in this case–control study. Clinical severity was evaluated by SCORing Atopic Dermatitis index. Serum level of IL-38 was measured by enzyme-linked immunosorbent assay for all participants. Also, peripheral eosinophilic count and total immunoglobulin E were measured in participating patients only.
Results IL-38 serum concentrations were extensively higher in atopic sufferers than controls (P<0.05). Moreover, there is a statistically significant correlation between IL-38 levels and both atopic severity and inflammatory markers as peripheral eosinophilic count and total immunoglobulin E.
Conclusion IL-38 represents a mirror for atopic severity and its inflammatory state.

Keywords: atopic dermatitis, cytokines, interleukin-38

How to cite this article:
Khattab FM, Khater EM, Ibraheem HA. Serum levels of interleukin-38 in sufferers with atopic eczema. Egypt J Dermatol Venerol 2019;39:66-70

How to cite this URL:
Khattab FM, Khater EM, Ibraheem HA. Serum levels of interleukin-38 in sufferers with atopic eczema. Egypt J Dermatol Venerol [serial online] 2019 [cited 2021 Feb 25];39:66-70. Available from: http://www.ejdv.eg.net/text.asp?2019/39/2/66/262033

  Introduction Top

Atopic dermatitis (AD) is a chronic eczematous skin disease characterized by elevated levels of T-helper 2 (Th2) cytokines, which include interleukin-4 (IL-4) and IL-5, high serum immunoglobulin E (IgE), peripheral blood eosinophilia, and positive immediate hypersensitivity to food or environmental allergens [1]. AD has a worldwide prevalence, especially among children since the incidence of childhood allergies is as much as 30% [2].

The IL-1 family is a cytokine group, which includes different members as IL-1β and IL-18 and IL-38 which is a new member. IL-38 has specific receptors as ST2 and IL-1RAcP [3]. ST2 is highly expressed on Th2 cells, mast cells, and eosinophils where IL-38 can bind to activate these cells and promote Th2-type specific immune responses [4]. Indeed, IL-38 is primarily expressed in keratinocytes and proliferating B-cells of the tonsil. Since, the amino acid homology of both IL-38 and the naturally existing IL-1 receptor antagonist (IL-1Ra) and the ability of IL-38 to bind with the soluble IL-1 receptor type I, it is hypothesized that IL-38 acts as an IL-1Ra [5],[6]. Even so, the binding affinity of IL-38 is significantly lower than that of IL-1Ra and IL-1β [7].

The allele combinations of IL-38 polymorphisms were found to be related to the risk of different diseases as psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and rheumatoid arthritis. These findings suggest that IL-38 plays an essential role in the pathogenesis of these inflammatory illnesses [8],[9].

The aim of this work is to detect the serum level of IL-38 in atopic patients and in healthy controls by enzyme-linked immunosorbent assay (ELISA) and to find if these levels correlate with the disease severity and different laboratory markers.

  Patients and methods‏‏ Top

Twenty-six AD patients (13 female and 13 men) fulfilled the Hanifin and Rajka criteria for diagnosis of AD were enrolled in this study. A patient who received systemic or local glucocorticoids within 1 month or 1 week, respectively, or a patient who had bacterial or virus infections within 2 weeks prior to the assessment were excluded. Furthermore, the patients were treated with other immunosuppressive agents or desensitization therapy within 6 months of entering the study. In addition to the patient group, 26 healthy volunteers who have not reported any family history or previous history of clinical atopy symptoms were recruited as a control group. The two groups were matched on age and sex. The disease severity was evaluated in patient group using SCORing Atopic Dermatitis (SCORAD) score (median score, 27.0; range, 5.8–58.4) [10]. Also, this group was divided according to SCORAD score into other three groups (mild, 0–24; moderate, 25–50; and severe, 51–103).

Five milliliters of venous blood was collected by venipuncture from every patient under complete aseptic technique and was divided into two tubes. Two milliliters of blood had been added to the EDTA solution for estimation of the entire blood photograph and the remaining blood sample was centrifuged for 10 min at 1500 rpm in order to separate the serum which is stored frozen at −20°C until complete collection of all samples.

Blood sample of each patient was examined to detect complete blood picture (differential leukocytes and absolute eosinophilic count), serum IgE by enzyme immune assay (normal range, 0–70) and serum concentrations of IL-38 via ELISA kits for quantitative analysis of IL-38.

Quantitative analysis of interleukin-38

Serum concentrations of IL-38 were measured by ELISA kits for quantitative detection of IL-38; reagents from Adipogen (Adipogen International, San Diego, California, USA). The reference range of the assay kit was from 0 to 1000 pg/ml. The sample, which fell outside this reference range, was re-analyzed at a higher dilution. The different measurements were performed in triplicates and the mean values were then determined.

Statistical analysis

After data collection, the data were tabled and analyzed using SPSS-19 (IBM Corp., Armonk, New York, USA). The following tests were used: a χ2 (v2), Student’s t test, Spearman’s correlation coefficient (r), and one-way analysis of variance. Differences were considered statistically significant (S) when P value less than 0.05, highly significant (HS) when P value less than 0.001 and nonsignificant (NS) when P value more than 0.05. A receiver operating characteristic curve analysis was conducted to evaluate the performance of the IL-38 assay for the prediction of active atopic disease. The sensitivity (true positive rate) and the specificity (true negative rate) were determined, and 95% confidence interval was obtained for each study and subsequently combined. The statistical analysis was based on the intention-to-treat population. Data were represented as mean±SD, range, numbers, or percentages.

  Results Top

Demographic data on all patients

This study included 26 atopic patients; their ages ranged from 10 to 65 years (mean±SD, 47±14.9) and the ratio of male to female was 1 : 1. They were also subdivided into mild (eight patients), moderate (nine patients), and severe (nine patients) according to SCORAD score for disease severity. The control group included 26 healthy individuals aged 12–65 years (mean±SD, 47.3±14.9 years), and the ratio of male to female was 1 : 1 ([Table 1]).
Table 1 Demographic data of the studied groups

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Serum levels of interleukin-38 in patients and controls

Using ELISA, IL-38 was measured in the serum of both patient and control groups and levels higher than 0.75 ng/ml were considered positive, according to the receiver operating characteristic curve. IL-38 levels ranged from 0.6 to 6.2 (mean±SD, 2.47±1.64) in the patient group, and from 0.01 to 1.5 (mean±SD, 0.61±0.49) in the control group. Thus, the difference in serum IL-38 levels was highly significant (P<0.001) between the patient and the control group ([Table 2]).
Table 2 Serum interleukin-38 levels among studied groups

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Relationship of interleukin-38 with disease severity and laboratory markers in patient group

A significant difference in IL-38 levels (P<0.001) was found among the disease severity subgroups ([Table 3]). Also, when comparing IL-38 levels in patients with positive and negative family history of atopic history, there was a significant difference (P=0.018 and P=0.02, respectively), as shown in [Table 4].
Table 3 Relation between severity of atopy and serum interleukin-38 levels in patient group

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Table 4 Family history of atopic dermatitis in patient groups and their relation to interleukin-38 levels

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Peripheral blood eosinophilic count (cells/mm3) and total IgE (IU/ml) were measured for both patients and controls. The range of eosinophilic count in the patient group was 6–37 (mean±SD, 25.69±8.25), while that in the control group was 2–8 (mean±SD, 5.08±1.83). Total IgE ranged from 5.1 to 9.2 (mean±SD, 6.97±1.24) in the patient group and from 2.8 to 4.8 (mean±SD, 3.78±0.58) in the control group. A highly significant difference between the patients and the controls was found in both markers (P<0.001) ([Table 5]).
Table 5 Peripheral blood eosinophilic count (cells/mm3) and total immunoglobulin E (IU/ml) levels among studied groups

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It should be noted that there was a statistically significant correlation between serum IL-38 and total IgE, eosinophilic count, and SCORAD score in AD patients (r=0.66, P<0.001; r=0.59, P<0.001; r=0.76, P<0.001, respectively) ([Table 6] and [Figure 1] and [Figure 2]).
Table 6 Correlation between serum interleukin-38 and other parameters in the patient group

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Figure 1 Peripheral blood eosinophilic count and total serum IgE levels in the studied groups. IgE, immunoglobulin E.

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Figure 2 Levels of IL-38 between healthy and atopic patients. IL-38, interleukin-38.

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  Discussion Top

In recent years, AD is well known to be associated with disorders of Th2 lymphocytes and the cytokines released by them. These cytokines include IL-4, IL-5, IL-9, IL-13, which play important roles in amplifying the inflammatory reaction of the skin, and both IL-6, IL-1β, which are involved in different inflammatory cascades [1].

The extended serum Th2 cytokine, IL-5, has additionally been observed in atopic sufferers despite the fact that IL-4 turned into as soon as undetectable. Other proinflammatory cytokines IL-17, IL-6, interferon-γ, and IL-1β have been also elevated in atopic patients [11]. IL-38 is a new member of the IL-1 cytokine family with a comparative feature of IL-36Ra. It may participate the network of IL-1 family members in regulating adaptive and innate immune responses [12].

The aim of this work was to estimate the serum level of IL-38 by ELISA in atopic patients and to detect its correlation with disease severity. In order to achieve this, the study was carried on 26 AD patients divided into mild, moderate, and severe according to SCORAD score, and 26 age-matched and sex-matched controls.

The serum IL-38 levels were significantly higher in the patient group compared to the control group (P<0.001). Chu et al. [13]‏ studied the production of IL-38 in asthmatic children and reported that its serum level was negatively correlated with Treg and IL-10 secretions, and positively correlated with IL-36R expression, suggesting a role for IL-38 in the pathogenesis of asthma‏.

In addition to that, there was a significant correlation with the SCORAD index and eosinophilic count (P<0.03). Our study shows not only similar results, but also shows the significant correlation between the clinical severity of AD and IgE levels [14].

The elevates IgE and eosinophilia found in the AD can also replicate elevated responses of Th2 cytokines. Elevation of serum IL-38 and relation with eosinophilic count and IgE levels may reflect increased responses of type Th2 cytokines [15].

Mercurio et al. [16], demonstrated that circulating IL-38 levels were reduced in skin diseases with neutrophilic infiltrate, so this can explain the elevation of IL-38 in AD that characterized by eosinophilic infiltrate.

IL-38 were increased in the epidermis of hidradenitis suppurativa, sweet syndrome, pyoderma gangrenosum, and AD, in relation to healthy control, with different localization among the disorders [17]. Immunoreactivity for IL-38 was highly detected throughout the epidermis of AD.

Also, IL-38 is highly expressed in psoriatic arthritis, which is an inflammatory disease often affects the peripheral joints and the skin [18].

Peripheral blood eosinophilic count and total IgE were measured in all patients and showed a significant (P<0.001) higher levels in patients than controls and a positive correlation with the disease severity. They are inflammatory markers reflecting the inflammatory condition of the skin and have been reported in AD [19].

Peripheral blood eosinophilic count and total IgE are nonspecific markers released in response to an allergic reaction. On the contrary, the IL-38 content in the sera of patients may be considered to reflect their level in atopic skin. The significant correlation of IL-38 with peripheral blood eosinophilic count and total IgE potentiates the role of IL-38 in acting as a mirror in atopic patients with more specificity than eosinophilic count and total IgE.

In our study, the increased circulating IL-38 was correlated with the severity of the SCORAD score. This may be by having anti-inflammatory effects, especially in modulating the Th17 response, making this cytokine of interest for targeting a large panel of autoimmune diseases.

  Conclusion Top

In conclusion, our results indicate that the IL-38 serum levels are elevated in AD patients and closely linked to the SCORAD score. These findings suggest that IL-38 is heavily involved in the pathomechanism of the AD, and that mechanical injury and barrier disruption can lead to IL-38 release. So, serum IL-38 levels may therefore be a useful indicator of the severity of AD.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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