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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
7. Izakovicova Holla L. Interleukin-18 in asthma and other allergies. Clin Exp Allergy. 2003; 33:1023–5.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
8. Chang TT, Stevens SR. Atopic dermatitis: the role of recombinant interferon-gamma therapy. Am J Clin Dermatol. 2002; 3:175–83.
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
12. Yoshizawa Y, Nomaguchi H, Izaki S, Kitamura K. Serum cytokine levels in atopic dermatitis. Clin Exp Dermatol. 2002; 27:225–9.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
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](/upload/SynapseXML/0039kjlm/thumb/kjlm-27-128f1.gif)
Table 1.
Characteristics of atopic dermatitis patients and healthy controls
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 |