Journal List > Korean J Lab Med > v.27(2) > 1011379

Park and Youn: Clinical Significance of Serum Interleukin-18 Concentration in the Patients with Atopic Dermatitis

Abstract

Background

Interleukin (IL)-18, a potent inducer of interferon gamma (FN-γ), is known to have a role in diseases involving type-2 T helper cell responses including atopic dermatitis. In this study, we aimed to determine the clinical significance of serum IL-18 level in the patients with atopic dermatitis.

Methods

Serum concentration of IL-18, IFN-γ, IgE, and blood eosinophil were measured in the patients with atopic dermatitis and healthy control subjects, and their association with the clinical score of the disease was analysed.

Results

Serum concentrations of IL-18 were significantly elevated in patients with atopic dermatitis compared to the healthy controls (332 pg/mL vs 151 pg/mL, P<0.05). Serum levels of IL-18 (r=0.41, P=0.001), eosinophil (r=0.36, P=0.003), and IgE (r=0.32, P=0.009) correlated with clinical scores in the patients. Also, multiple regression analysis indicated that serum IL-18 and IgE levels were independent predictors for the clinical score of atopic dermatitis (r2=0.25, β=0.39, P=0.001 and β=0.32, P=0.009).

Conclusions

Our results confirmed a significant correlation between the concentration of serum IL-18 and the severity of atopic dermatitis. Although serum IL-18 concentration reflects the disease severity, its usefulness as a clinical test needs to be further investigated, because its additive benefit over those of conventional blood tests is not evident so far.

References

1. Okamura H, Tsutsui H, Kashiwamura S, Yoshimoto T, Nakanishi K. Interleukin-18: a novel cytokine that augments both innate and acquired immunity. Adv Immunol. 1998; 70:281–312.
crossref
2. Billiau A. Interferon-gamma: biology and role in pathogenesis. Adv Immunol. 1996; 62:61–130.
3. Xu L, Rothman P. IFN-gamma represses epsilon germline transcription and subsequently down-regulates switch recombination to epsilon. Int Immunol. 1994; 6:515–21.
4. Pizarro TT, Michie MH, Bentz M, Woraratanadharm J, Smith MF Jr, Foley E, et al. IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. J Immunol. 1999; 162:6829–35.
crossref
5. Gracie JA, Forsey RJ, Chan WL, Gilmour A, Leung BP, Greer MR, et al. A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest. 1999; 104:1393–401.
crossref
6. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol. 2001; 19:423–74.
crossref
7. Izakovicova Holla L. Interleukin-18 in asthma and other allergies. Clin Exp Allergy. 2003; 33:1023–5.
crossref
8. Chang TT, Stevens SR. Atopic dermatitis: the role of recombinant interferon-gamma therapy. Am J Clin Dermatol. 2002; 3:175–83.
9. Kang K, Stevens SR. Pathophysiology of atopic dermatitis. Clin Dermatol. 2003; 21:116–21.
crossref
10. Wild JS, Sigounas A, Sur N, Siddiqui MS, Alam R, Kurimoto M, et al. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J Immunol. 2000; 164:2701–10.
11. Konishi H, Tsutsui H, Murakami T, Yumikura-Futatsugi S, Yamanaka K, Tanaka M, et al. IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. Proc Natl Acad Sci USA. 2002; 99:11340–5.
crossref
12. Yoshizawa Y, Nomaguchi H, Izaki S, Kitamura K. Serum cytokine levels in atopic dermatitis. Clin Exp Dermatol. 2002; 27:225–9.
crossref
13. Hon KL, Leung TF, Ma KC, Wong CK, Wan H, Lam CW. Serum concentration of IL-18 correlates with disease extent in young children with atopic dermatitis. Pediatr Dermatol. 2004; 21:619–22.
crossref
14. Aral M, Arican O, Gul M, Sasmaz S, Kocturk SA, Kastal U, et al. The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis. Mediators Inflamm. 2006; 2006:73098.
15. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venererol. 1980; 92:44–7.
16. Stadler JF. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993; 186:23–31.
17. Tanaka T, Tsutsui H, Yoshimoto T, Kotani M, Matsumoto M, Fujita A, et al. Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga. Int Arch Allergy Immunol. 2001; 125:236–40.
crossref
18. El-Mezzein RE, Matsumoto T, Nomiyama H, Miike T. Increased secretion of IL-18 in vitro by peripheral blood mononuclear cells of patients with bronchial asthma and atopic dermatitis. Clin Exp Immunol. 2001; 126:193–8.
crossref
19. Yoon DY, Lee KA, Park JK, Kim JW. Determination and significance of serum Interleukin-18 levels in patients with chronic hepatitis B virus infection. Korean J Lab Med. 2004; 24:139–45.

Fig. 1.
Mean concentrations (rectangles) and 95% confidence intervals (error bars) of blood eosinophil, IgE, IL-18, and IFN-γ in healthy controls, total atopic dermatitis (AD), and each disease grade group (mild, moderate, and severe) of AD.
kjlm-27-128f1.tif
Fig. 2.
ROC curve analysis for the screening efficiency of serum IL-18.
kjlm-27-128f2.tif
Table 1.
Characteristics of atopic dermatitis patients and healthy controls
  Atopic dermatitis (SCORAD range)
Controls
Total Mild (<25) Moderate (25–50) Severe (>50)
Number 65 15 20 30 61
Age (yr) 15±10 14±8 14±9 17±10 19±7
  (2–41) (6–37) (2–30) (2–41) (3–39)
Sex (M/F) 43/22 9/6 11/9 23/7 40/21
SCORAD 45 19 36 63  
index (40–50) (18–21) (34–39) (59–67)  

Age (yr) is shown as the mean±1SD and range. The levels of SCO-RAD index are presented as mean and 95% confidence interval for mean.

Abbreviation: NS, not significant.

Table 2.
Correlation among clinical severity and blood markers evaluated by Pearson correlation
    SCORAD IL-18 Eosinophil counts IgE
IL18 r 0.41      
  P 0.001*      
Eosinophil counts r 0.36 0.41    
  P 0.003* 0.001*    
IgE r 0.32 0.01 0.13  
  P 0.009* NS NS  
INF-γ r 0.07 0.02 0.16 0.13
  P NS NS NS NS

* P<0.05.

Abbreviation: NS, not significant.

Table 3.
Multiple linear regression analysis evaluating the independent factors for clinical severity of atopic dermatitis patients
Model r2 Predictor SCORAD Coefficients (β) P
A 0.16 IL-18 0.39 0.002
B 0.25 IL-18 0.39 0.001
    IgE 0.32 0.009

Excluded variables are age, sex, eosinophil, IgE, and IFN-r in model A; and age, sex, eosinophil, and IFN-γ in model B by stepwise linear regression.

TOOLS
Similar articles