Background:  Staphylococcus aureus colonization has been found in 80–100% of lesional skin from patients with atopic eczema dermatitis syndrome (AEDS) and is thought to have a role in the pathogenesis of the disease. Furthermore, up to 65% of S. aureus from lesional skin has been shown to produce toxigenic superantigens. Methods: Using a cohort of 11 children under 2 years of age diagnosed with AEDS, we isolated peripheral blood mononuclear cells, cultured them with staphylococcal enterotoxin B (SEB) and phytohaemagglutinin, and assessed the cytokine response profiles. Plasma was also collected for immunoglobulin E analysis. In addition, skin and nasal swabs were taken and cultured to determine the presence of SEB-producing S. aureus by polymerase chain reaction (PCR) and reverse passive latex agglutination. Results: We found a significant increase in the production of the SEB-induced cytokines interleukin (IL)-5 and IL-13 in the patient group when compared with non-atopic, healthy controls. For IL-13, there was almost no overlap in the levels between the groups. However, there was no correlation between SEB-induced IL-13 and disease severity. This difference was not seen when heat-inactivated S. aureus was used to stimulate the cells. Conclusions: IL-13 is an important factor in AEDS development in early childhood, and prophylactic anti-staphylococcal treatment may provide protection from AEDS in atopic individuals.

Keywords:
Interleukin-13, Atopic dermatitis, Staphylococcal enterotoxin B
1.
Foley P, Zuo Y, Plunkett A, Marks R: The frequency of common skin conditions in preschool-age children in Australia: Atopic dermatitis. Arch Dermatol 2001;137:293–300.
2.
Leung DY: Atopic dermatitis: Immunobiology and treatment with immune modulators. Clin Exp Immunol 1997;107(suppl 1):25–30.
3.
Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wuthrich B: A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001;56:813–824.
4.
Leung DY: Atopic dermatitis: New insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 2000;105:860–876.
5.
Holt PG, Macaubas C: Development of long-term tolerance versus sensitisation to environmental allergens during the perinatal period. Curr Opin Immunol 1997;9:782–787.
6.
Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K: Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica 1985;170:35–39.
7.
Hoeger PH, Lenz W, Boutonnier A, Fournier JM: Staphylococcal skin colonization in children with atopic dermatitis: Prevalence, persistence, and transmission of toxigenic and nontoxigenic strains. J Infect Dis 1992;165:1064–1068.
8.
Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G, Wahn U, Renz H: Evidence for a disease-promoting effect of Staphylococcus aureus- derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 2000;105:814–819.
9.
Zollner TM, Wichelhaus TA, Hartung A, Von Mallinckrodt C, Wagner TO, Brade V, Kaufmann R: Colonization with superantigen-producing Staphylococcus aureus is associated with increased severity of atopic dermatitis. Clin Exp Allergy 2000;30:994–1000.
10.
Arad G, Levy R, Kaempfer R: Superantigen concomitantly induces Th1 cytokine genes and the ability to shut off their expression on re-exposure to superantigen. Immunol Lett 2002;82:75–78.
11.
Heaton T, Mallon D, Venaille T, Holt P: Staphylococcal enterotoxin induced IL-5 stimulation as a cofactor in the pathogenesis of atopic disease: The hygiene hypothesis in reverse? Allergy 2003;58:252–256.
12.
Hoeger PH, Ganschow R, Finger G: Staphylococcal septicemia in children with atopic dermatitis. Pediatr Dermatol 2000;17:111–114.
13.
Hanifin JM, Rajka G: Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980;92:44–47.
14.
Kunz B, Oranje AP, Labreze L, Stalder JF, Ring J, Taieb A: Clinical validation and guidelines for the SCORAD index: Consensus report of the European Task Force on atopic dermatitis. Dermatology 1997;195:10–19.
15.
Sharp MJ, Rowe J, Kusel M, Sly PD, Holt PG: Specific patterns of responsiveness to microbial antigens staphylococcal enterotoxin B and purified protein derivative by cord blood mononuclear cells are predictive of risk for development of atopic dermatitis. Clin Exp Allergy 2003;33:435–441.
16.
Emson CL, Bell SE, Jones A, Wisden W, McKenzie AN: Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. J Exp Med 1998;188:399–404.
17.
Punnonen J, Yssel H, de Vries JE: The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells. J Allergy Clin Immunol 1997;100:792–801.
18.
Ohshima Y, Yasutomi M, Omata N, Yamada A, Fujisawa K, Kasuga K, Hiraoka M, Mayumi M: Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants. Pediatr Res 2002;51:195–200.
19.
Ribeiro-do-Couto LM, Boeije LC, Kroon JS, Hooibrink B, Breur-Vriesendorp BS, Aarden LA, Boog CJ: High IL-13 production by human neonatal T cells: Neonate immune system regulator? Eur J Immunol 2001;31:3394–3402.
20.
Katagiri K, Itami S, Hatano Y, Takayasu S: Increased levels of IL-13 mRNA, but not IL-4 mRNA, are found in vivo in peripheral blood mononuclear cells (PBMC) of patients with atopic dermatitis (AD). Clin Exp Immunol 1997;108:289–294.
21.
Aleksza M, Lukacs A, Antal-Szalmas P, Hunyadi J, Szegedi A: Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis. Br J Dermatol 2002;147:1135–1141.
22.
Simon D, Borelli S, Braathen LR, Simon HU: Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-gamma. Allergy 2002;57:431–435.
23.
Smart JM, Kemp AS: Ontogeny of T-helper 1 and T-helper 2 cytokine production in childhood. Pediatr Allergy Immunol 2001;12:181–187.
24.
Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG: Development of allergen-specific T-cell memory in atopic and normal children. Lancet 1999;353:196–200.
25.
Ha SJ, Lee HJ, Byun DG, Kim JW: Expression of T cell receptor V beta chain in lesional skin of atopic dermatitis. Acta Derm Venereol 1998;78:424–427.
26.
Campbell DE, Kemp AS: Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response to Staphylococcus aureus and staphylococcal superantigen in childhood atopic dermatitis. Clin Exp Immunol 1997;107:392–397.
27.
Smart JM, Tang ML, Kemp AS: Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease. Clin Exp Allergy 2002;32:1552–1557.
28.
Miller SJ, Aly R, Shinefeld HR, Elias PM: In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids. Arch Dermatol 1988;124:209–215.
29.
Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T: Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002;118:275–281.
30.
Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY: Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 2003;171:3262–3269.
31.
Breuer K, Haussler S, Kapp A, Werfel T: Staphylococcus aureus: Colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 2002;147:55–61.
32.
Matsui K, Nishikawa A, Suto H, Tsuboi R, Ogawa H: Comparative study of Staphylococcus aureus isolated from lesional and non-lesional skin of atopic dermatitis patients. Microbiol Immunol 2000;44:945–947.
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2004
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