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Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis

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Abstract

Background

Although both interleukin-4 (IL-4) and IL-13 induce immunoglobulin E (IgE) production in vitro, the relative contribution of the two cytokines in various skin lesions of atopic dermatitis remains unclear.

Objective

We examined the relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis for IgE production.

Methods

The study group comprised 28 atopic dermatitis patients with serum IgE levels more than 2000 IU/ml. The expression levels of IL-4 mRNA and IL-13 mRNA versus that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) method in samples of normal-appearing skin from seven patients, very mild lesions from eight patients, subacute lesions from ten patients and lichenified lesions from ten patients with atopic dermatitis, and in samples of normal skin from six healthy control subjects.

Results

IL-4 mRNA expression was identified in only two of the eight very mild lesions, one of the ten subacute lesions, and none of the ten lichenified lesions, whereas IL-13 mRNA expression was identified in 27 of the 28 skin lesions of atopic dermatitis. The IL-13 mRNA/GAPDH mRNA ratios (×100) in the subacute lesions (94.4±20.6) and lichenified lesions (71.4±40.4) were significantly greater than in the skin of healthy controls (13.1±17.7; P<0.01, P<0.05, respectively).

Conclusions

Upregulation of IL-13 mRNA in subacute and chronic lesions of atopic dermatitis along with scant expression of IL-4 mRNA suggest that IL-13 is a crucial cytokine in lesional skin.

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References

  1. Tanaka K, Sugiura H, Uehara M, Hashimoto Y, Donnelly C, Montgomery DS (2001) Lack of association between atopic eczema and the genetic variants of interleukin-4 and the interleukin-4 receptor α chain gene: heterogeneity of genetic backgrounds on immunoglobulin E production in atopic eczema patients. Clin Exp Allergy 31:1522–1527

    Article  CAS  PubMed  Google Scholar 

  2. Graves PE, Kabesch M, Halonen M, Holberg CJ, Baldini M, Fritzsch C, Weiland SK, Erickson RP, von Mutius E, Martinez FD (2000) A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol 105:506–513

    CAS  PubMed  Google Scholar 

  3. Punnonen J, Yessel H, de Vries JE (1997) 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 100:792–801

    CAS  PubMed  Google Scholar 

  4. Shirakawa T, Deichmann KA, Izuhara K, Mao X-Q, Adra CN, Hopkin JM (2000) Atopy and asthma: genetic variants of IL-4 and IL-13 signalling. Immunol Today 21:60–64

    Article  CAS  PubMed  Google Scholar 

  5. Katagiri K, Itami S, Hatano Y, Takayasu S (1997) 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 108:289–294

    Article  CAS  PubMed  Google Scholar 

  6. Hamid Q, Boguniewicz M, Leung DY (1994) Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest 94:870–876

    CAS  PubMed  Google Scholar 

  7. Van der Ploeg I, Jeddi Tehrani M, Matuseviciene G, Wahlgren CF, Fransson J, Scheynius A (1997) IL-13 over-expression in skin is not confined to IgE-mediated skin inflammation. Clin Exp Immunol 109:526–532

    Article  PubMed  Google Scholar 

  8. Williams HC, Burney PGJ, Pembroke AC, Hay RJ (1994) The UK Working Party’s Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation. Br J Dermatol 131:406–416

    CAS  PubMed  Google Scholar 

  9. Hanifin JM, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 92:44–47

    Google Scholar 

  10. Ueno H, Nakamura H, Inoue M, Imai K, Noguchi M, Sato H, Seiki M, Okada Y (1997) Expression and tissue localization of membrane-type 1, 2 and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 57:2055–2060

    CAS  PubMed  Google Scholar 

  11. Watts D, MacBeath JRE (2001) Automated fluorescent DNA sequencing on the ABI PRISM 310 Genetic Analyzer. Methods Mol Biol 167:153–170

    Article  CAS  PubMed  Google Scholar 

  12. Yokota T, Otsuka T, Mosmann T, Banchereau J, DeFrance T, Blanchard D, De Vries JE, Lee F, Arai K (1986) Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities. Proc Natl Acad Sci U S A 83:5894–5898

    CAS  PubMed  Google Scholar 

  13. McKenzie AN, Culpepper JA, de Waal Malefyt R, Briere F, Punnonen J, Aversa G, Sato A, Dang W, Cocks BG, Menon S (1993) Interleukin-13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci U S A 90:3735–3739

    CAS  PubMed  Google Scholar 

  14. Pawankar RU, Okuda M, Hasegawa S, Suzuki K, Yssel H, Okubo K, Okumura K, Ra C (1995) Interleukin-13 expression in the nasal mucosa of perennial allergic rhinitis. Am J Respir Crit Care Med 152:2059–2067

    CAS  PubMed  Google Scholar 

  15. Yu RC, Abrams DC, Alaibac M, Chu AC (1994) Morphological and quantitative analyses of normal epidermal Langerhans cells using confocal scanning laser microscopy. Br J Dermatol 131:843–848

    CAS  PubMed  Google Scholar 

  16. Tang M, Kemp A, Varigos G (1993) IL-4 and interferon-gamma production in children with atopic disease. Clin Exp Immunol 92:120–124

    CAS  PubMed  Google Scholar 

  17. Jujo K, Renz H, Abe J, Gelfand EW, Leung DYM (1992) Decreased interferon-gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy Clin Immunol 90:323–331

    CAS  PubMed  Google Scholar 

  18. Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Ehrlich-Kautzky E, Schou C, Krishnaswamy G, Beaty TH (1994) Linkage analysis of IL-4 and other chromosome 5p31.1 markers and total serum immunoglobulin E concentration. Science 264:1152–1156

    CAS  PubMed  Google Scholar 

  19. Rosenwasser LJ, Borish L (1997) Genetics of atopy and asthma: the relation behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med 160:19–22

    Google Scholar 

  20. Van der Ploeg I, Tengvall Linder M, Hagermark O, Wahlgren CF, Scheynius A (1996) Differential gene expression for interleukin-13 and other cytokines in the skin of atopic dermatitis patients and healthy subjects. Adv Exp Med Biol 409:403–404

    PubMed  Google Scholar 

  21. Grewe M, Walther S, Gyufko K, Czech W, Schöpf E, Krutmann J (1995) Analysis of the cytokine pattern expression in situ in inhalant allergen patch test reaction of atopic dermatitis patients. J Invest Dermatol 105:407–410

    CAS  PubMed  Google Scholar 

  22. Bradding P, Feather IH, Wilson S, Bardin PG, Heusser CH, Holgate T, Howarth PH (1993) Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J Immunol 151:3853–3865

    CAS  PubMed  Google Scholar 

  23. Macleod JD, Anderson DF, Baddeley SM, Holgate ST, Mcgill JI, Roche WR (1997) Immunolocalization of cytokines to mast cells in normal and allergic conjunctiva. Clin Exp Allergy 27:1328–1334

    Article  CAS  PubMed  Google Scholar 

  24. Akdis CA, Akdis M, Simon D, Dibbert B, Weber M, Gratzl S, Kreyden O, Disch R, Wüthrich B, Blaster K, Simon HU (1999) T cells and T cell-derived cytokines as pathogenic factors in the nonallergic form of atopic dermatitis. J Invest Dermatol 113:628–634

    Article  CAS  PubMed  Google Scholar 

  25. Horsmanheimo L, Harvima IT, Järvikallio A, Harvima RJ, Naukkarinen A, Horsmanheimo M (1994) Mast cells are one major source of interleukin-4 in atopic dermatitis. Br J Dermatol 131:348–353

    CAS  PubMed  Google Scholar 

  26. de Saint-Vis B, Fugier-Vivier I, Massacrier C, Gaillard C, Vanbervliet B, Ait-Yahia S, Banchereau J, Liu YJ, Lebecque S, Caux C (1998) The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J Immunol 160:1666–1676

    PubMed  Google Scholar 

  27. Grewe M, Gyufko K, Schöpf E, Krutmann J (1994) Lesional expression of interferon-γ in atopic dermatitis. Lancet 343:25–26

    CAS  PubMed  Google Scholar 

  28. de Waal-Malefyt R, Abrams JS, Zurawski SM, Lecron JC, Mohan-Peterson S, Sanjanwala B, Bennett B, Silver J, de Vries JE, Yssel H (1995) Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells. Int Immunol 7:1405–1416

    PubMed  Google Scholar 

  29. Johnson EE, Irons JS, Patterson R (1974) Serum IgE concentration in atopic dermatitis. J Allergy Clin Immunol 54:94–99

    CAS  PubMed  Google Scholar 

  30. Jones HE, Inouye JC, McGerity JL, Lewis CW (1975) Atopic disease and serum immunoglobulin-E. Br J Dermatol 92:17–25

    CAS  PubMed  Google Scholar 

  31. Uehara M (1989) Family background of respiratory atopy: a factor of serum IgE elevation in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 144:78–82

    Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Dermatology, Shiga University of Medical Science, Seta Tsukinowa-cho, 520-2192, Otsu, Japan

    Takahiro Tazawa, Hisashi Sugiura & Masami Uehara

  2. 2nd Expert Service Division, Bureau of International Cooperation, International Medical Center of Japan, Ministry of Health, Labour and Welfare, 1-21-1 Toyama, Shinjuku, 162-8655, Tokyo, Japan

    Yasuo Sugiura

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  1. Takahiro Tazawa
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  2. Hisashi Sugiura
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  3. Yasuo Sugiura
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  4. Masami Uehara
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Correspondence to Hisashi Sugiura.

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Tazawa, T., Sugiura, H., Sugiura, Y. et al. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res 295, 459–464 (2004). https://doi.org/10.1007/s00403-004-0455-6

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  • DOI: https://doi.org/10.1007/s00403-004-0455-6

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