IL-4 and IL-12 polymorphisms are associated with response to suplatast tosilate, a Th2 cytokine inhibitor, in patients with atopic dermatitis

Hideki Nagase, Yoshinori Nakachi, Keiji Ishida, Mamoru Kiniwa, Satoshi Takeuchi, Ichiro Katayama, Yoshinari Matsumoto, Fukumi Furukawa, Shin Morizane, Sakae Kaneko, Yoshiki Tokura, Motoi Takenaka, Yutaka Hatano, Yoshiki Miyachi

Research output: Contribution to journalArticle

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Abstract

Th2-related immune and inflammatory responses have been implicated in the pathogenesis of atopic dermatitis (AD), but few clinical lines of evidence have been reported regarding how and whether Th2-related responses are associated with other risk factors in the treatment of AD patients. In this study, the associations between the polymorphisms of genes related to the pathophysiology of AD and the efficacy of suplatast tosilate, an oral immunemodulator known to downregulate Th2-related allergic responses, were analyzed in adult patients with chronic AD. Patients were recruited from our previous study, where suplatast tosilate was evaluated for its efficacy when used in combination with topical steroids. The genotypes of 35 single nucleotide polymorphisms (SNPs) of 27 genes related to AD pathogenesis were then determined in 17 responders and 18 non-responders, as defined by the improvement rate in their AD skin scores. While no significant difference in the patient background was observed between responders and non-responders, significant associations were noted between the response to treatment with suplatast tosilate and three SNPs of IL-4 (-590C/T: P=0.04, -33C/T: P=0.04) and IL-12B (1188A/C: P=0.03), but not for the other SNPs. Of note, ethnic differences in the genotype frequencies of IL-4 -590C/T and IL-12B 1188A/C SNPs were found. In conclusion, the present results raise the possibility that AD patients who tend to produce more IL-4 and IL-12 may be susceptible to suplatast tosilate treatment and that ethnic variations should be considered to further understand the role of Th2-related responses.

Original languageEnglish
Pages (from-to)42-50
Number of pages9
JournalOpen Dermatology Journal
Volume6
Issue number1
DOIs
Publication statusPublished - 2012

Fingerprint

Atopic Dermatitis
Interleukin-12
Interleukin-4
Cytokines
Single Nucleotide Polymorphism
Genotype
suplatast tosilate
Genes
Therapeutics
Down-Regulation
Steroids
Skin

Keywords

  • Atopic dermatitis
  • Ethnic difference
  • IL-12B
  • IL-4
  • Single nucleotide polymorphism
  • Suplatast tosilate
  • Th1
  • Th2

ASJC Scopus subject areas

  • Dermatology

Cite this

IL-4 and IL-12 polymorphisms are associated with response to suplatast tosilate, a Th2 cytokine inhibitor, in patients with atopic dermatitis. / Nagase, Hideki; Nakachi, Yoshinori; Ishida, Keiji; Kiniwa, Mamoru; Takeuchi, Satoshi; Katayama, Ichiro; Matsumoto, Yoshinari; Furukawa, Fukumi; Morizane, Shin; Kaneko, Sakae; Tokura, Yoshiki; Takenaka, Motoi; Hatano, Yutaka; Miyachi, Yoshiki.

In: Open Dermatology Journal, Vol. 6, No. 1, 2012, p. 42-50.

Research output: Contribution to journalArticle

Nagase, H, Nakachi, Y, Ishida, K, Kiniwa, M, Takeuchi, S, Katayama, I, Matsumoto, Y, Furukawa, F, Morizane, S, Kaneko, S, Tokura, Y, Takenaka, M, Hatano, Y & Miyachi, Y 2012, 'IL-4 and IL-12 polymorphisms are associated with response to suplatast tosilate, a Th2 cytokine inhibitor, in patients with atopic dermatitis', Open Dermatology Journal, vol. 6, no. 1, pp. 42-50. https://doi.org/10.2174/1874372201206010042
Nagase, Hideki ; Nakachi, Yoshinori ; Ishida, Keiji ; Kiniwa, Mamoru ; Takeuchi, Satoshi ; Katayama, Ichiro ; Matsumoto, Yoshinari ; Furukawa, Fukumi ; Morizane, Shin ; Kaneko, Sakae ; Tokura, Yoshiki ; Takenaka, Motoi ; Hatano, Yutaka ; Miyachi, Yoshiki. / IL-4 and IL-12 polymorphisms are associated with response to suplatast tosilate, a Th2 cytokine inhibitor, in patients with atopic dermatitis. In: Open Dermatology Journal. 2012 ; Vol. 6, No. 1. pp. 42-50.
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abstract = "Th2-related immune and inflammatory responses have been implicated in the pathogenesis of atopic dermatitis (AD), but few clinical lines of evidence have been reported regarding how and whether Th2-related responses are associated with other risk factors in the treatment of AD patients. In this study, the associations between the polymorphisms of genes related to the pathophysiology of AD and the efficacy of suplatast tosilate, an oral immunemodulator known to downregulate Th2-related allergic responses, were analyzed in adult patients with chronic AD. Patients were recruited from our previous study, where suplatast tosilate was evaluated for its efficacy when used in combination with topical steroids. The genotypes of 35 single nucleotide polymorphisms (SNPs) of 27 genes related to AD pathogenesis were then determined in 17 responders and 18 non-responders, as defined by the improvement rate in their AD skin scores. While no significant difference in the patient background was observed between responders and non-responders, significant associations were noted between the response to treatment with suplatast tosilate and three SNPs of IL-4 (-590C/T: P=0.04, -33C/T: P=0.04) and IL-12B (1188A/C: P=0.03), but not for the other SNPs. Of note, ethnic differences in the genotype frequencies of IL-4 -590C/T and IL-12B 1188A/C SNPs were found. In conclusion, the present results raise the possibility that AD patients who tend to produce more IL-4 and IL-12 may be susceptible to suplatast tosilate treatment and that ethnic variations should be considered to further understand the role of Th2-related responses.",
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AU - Ishida, Keiji

AU - Kiniwa, Mamoru

AU - Takeuchi, Satoshi

AU - Katayama, Ichiro

AU - Matsumoto, Yoshinari

AU - Furukawa, Fukumi

AU - Morizane, Shin

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AU - Hatano, Yutaka

AU - Miyachi, Yoshiki

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AB - Th2-related immune and inflammatory responses have been implicated in the pathogenesis of atopic dermatitis (AD), but few clinical lines of evidence have been reported regarding how and whether Th2-related responses are associated with other risk factors in the treatment of AD patients. In this study, the associations between the polymorphisms of genes related to the pathophysiology of AD and the efficacy of suplatast tosilate, an oral immunemodulator known to downregulate Th2-related allergic responses, were analyzed in adult patients with chronic AD. Patients were recruited from our previous study, where suplatast tosilate was evaluated for its efficacy when used in combination with topical steroids. The genotypes of 35 single nucleotide polymorphisms (SNPs) of 27 genes related to AD pathogenesis were then determined in 17 responders and 18 non-responders, as defined by the improvement rate in their AD skin scores. While no significant difference in the patient background was observed between responders and non-responders, significant associations were noted between the response to treatment with suplatast tosilate and three SNPs of IL-4 (-590C/T: P=0.04, -33C/T: P=0.04) and IL-12B (1188A/C: P=0.03), but not for the other SNPs. Of note, ethnic differences in the genotype frequencies of IL-4 -590C/T and IL-12B 1188A/C SNPs were found. In conclusion, the present results raise the possibility that AD patients who tend to produce more IL-4 and IL-12 may be susceptible to suplatast tosilate treatment and that ethnic variations should be considered to further understand the role of Th2-related responses.

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