• Users Online: 323
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
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
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_2_18

Rights and Permissions
  Abstract 


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 2019 Sep 16];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

Click here to view


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

Click here to view


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

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

Click here to view


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

Click here to view


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

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

Click here to view
Figure 2 Levels of IL-38 between healthy and atopic patients. IL-38, interleukin-38.

Click here to view



  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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Leung D, Boguniewicz M, Howell MD, Nomura I, Hamid Q. New insights into atopic dermatitis. J Clin Invest 2004; 113:1070.  Back to cited text no. 1
    
2.
Akdis C, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P et al. Diagnosis and treatment of atopic dermatitis in children and adults. J Allergy Clin Immunol 2006; 61:969–987.  Back to cited text no. 2
    
3.
Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117:3720–3732.  Back to cited text no. 3
    
4.
Dinarello C, Arend W, Sims J. IL-1 family nomenclature. Nat Immunol 2010; 11:973.  Back to cited text no. 4
    
5.
Guo ZS, Li C, Lin ZM, Huang XJ, Wei QJ, Wang XW et al. Association of IL-1 gene complex members with ankylosing spondylitis in the Chinese Han population. Int J Immunogenet 2010; 37:33–37.  Back to cited text no. 5
    
6.
Lin H, Ho AS, Haley-Vicente E. Cloning and characterization of IL-1HY2, a novel interleukin-1 family member. J Biol Chem 2001; 276:20597–20602.  Back to cited text no. 6
    
7.
Rahman P, Sun S, Peddle L, Snelgrove T, Miley W, Greenwood C, Gladman D. Association between the interleukin-1 family gene cluster and psoriatic arthritis. Arthritis Rheum 2006; 54:2321–2325.  Back to cited text no. 7
    
8.
Van de Veerdonk FL, Stoeckman AK, Wu G, Boeckermann AN, Azam T, Netea MG et al. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. Proc Natl Acad Sci USA 2012; 109:3001–3005.  Back to cited text no. 8
    
9.
Rudloff I, Godsell J, Nold-Petry CA, Harris J, Hoi A, Morand EF, Nold MF. Brief report: interleukin-38 exerts antiinflammatory functions and is associated with disease activity in systemic lupus erythematosus. Arthritis Rheumatol 2015; 67:3219–3225.  Back to cited text no. 9
    
10.
Ghanem A, Khattab F, Zidan A. Evaluation of serum periostin level in atopic dermatitis patients. Al-Azhar Assiut Med J 2017; 15:223–227.  Back to cited text no. 10
  [Full text]  
11.
Van Oosterhout AJ, Bloksma N. Regulatory T-lymphocytes in asthma. Eur Respir J 2005; 26:918–932.  Back to cited text no. 11
    
12.
Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol 2005; 116:961–968.  Back to cited text no. 12
    
13.
Chu M, Chu IM, Yung EC, Lam CW, Leung TF, Wong GW, Wong CK. Aberrant expression of novel cytokine IL-38 and regulatory T lymphocytes in childhood asthma. Molecules 2016; 21:piiE933.  Back to cited text no. 13
    
14.
Dhar S, Malakar R, Chattopadhyay S, Dhar S, Banerjee R, Ghosh A. Correlation of the severity of atopic dermatitis with absolute eosinophil counts in peripheral blood and serum IgE levels. Indian J Dermatol Venereol Leprol 2005; 71:246–249.  Back to cited text no. 14
[PUBMED]  [Full text]  
15.
Sanjuan MA, Sagar D, Kolbeck R. Role of IgE in autoimmunity. J Allergy Clin Immunol 2016; 137:1651–1661.  Back to cited text no. 15
    
16.
Mercurio L, Morelli M, Scarponi C, Eisenmesser EZ, Doti N, Pagnanelli G et al. IL-38 has an anti-inflammatory action in psoriasis and its expression correlates with disease severity and therapeutic response to anti-IL-17A treatment. Cell Death Dis 2018; 9:1104.  Back to cited text no. 16
    
17.
Yuan X, Peng X, Li Y, Li M. Role of IL-38 and its related cytokines in inflammation. Mediators Inflamm 2015; 2015:807976.  Back to cited text no. 17
    
18.
Garraud T, Harel M, Boutet MA, Le Goff B, Blanchard F. The enigmatic role of IL-38 in inflammatory diseases. Cytokine Growth Factor Rev 2018; 39:26–35.  Back to cited text no. 18
    
19.
Della Torre E, Mattoo H, Mahajan VS, Carruthers M, Pillai S, Stone JH. Prevalence of atopy, eosinophilia, and IgE elevation in IgG4-related disease. Allergy 2014; 69:269–272.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

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



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and met...
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed245    
    Printed24    
    Emailed0    
    PDF Downloaded47    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]