RESEARCH ARTICLE
IL-4 and IL-12 Polymorphisms are Associated with Response to Suplatast Tosilate, a Th2 Cytokine Inhibitor, in Patients with Atopic Dermatitis
Hideki Nagase1, Yoshinori Nakachi1, Keiji Ishida1, Mamoru Kiniwa*, 1, Satoshi Takeuchi2, Ichiro Katayama3, Yoshinari Matsumoto4, Fukumi Furukawa5, Shin Morizane6, Sakae Kaneko7, Yoshiki Tokura8, Motoi Takenaka9, Yutaka Hatano10, Yoshiki Miyachi11
Article Information
Identifiers and Pagination:
Year: 2012Volume: 6
First Page: 42
Last Page: 50
Publisher ID: TODJ-6-42
DOI: 10.2174/1874372201206010042
Article History:
Received Date: 23/08/2012Revision Received Date: 17/10/2012
Acceptance Date: 19/10/2012
Electronic publication date: 11/12/2012
Collection year: 2012
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
