Sadakane Kaori, Ichinose Takamichi, Takano Hirohisa, Yanagisawa Rie, Koike Eiko, Inoue Ken-ichiro
Department of Health Sciences, Oita University of Nursing and Health Sciences, Megusuno, Oita City, Oita, Japan.
J Appl Toxicol. 2014 Aug;34(8):893-902. doi: 10.1002/jat.2911. Epub 2013 Aug 23.
Phthalate esters in plastics act as adjuvants for immunoglobulin production, which aggravates allergic disease. However, the effects of alkylphenols (used as plasticizers and surfactants) on atopic dermatitis have not been studied in detail. Therefore, the goal of the present study was to investigate the effects of the alkylphenols 4-nonylphenol (NP), 4-tert-octylphenol (OP) and 4-tert-butylphenol (BP) in a murine model of atopic dermatitis. NC/Nga mice were intraperitoneally administered NP, OP or BP and were subcutaneously injected with mite allergen in one ear to induce atopic dermatitis-like skin lesions (ADSLs). The condition of the skin was observed, and the levels of immunoglobulin in serum and inflammatory cytokines in lesions were determined. NP exacerbated mite allergen-induced ADSLs according to dose. OP and BP also significantly exacerbated skin lesions but not as a function of dose. Alkylphenols tended to increase the levels of IgE and antigen-specific IgG1 in serum. Further, the treatment of the alkylphenols increased the expression in lesions of inflammatory cytokines, interleukin-4 and monocyte chemotactic protein-3. Thymic stromal lymphopoietin levels increased according to ADSL severity. In contrast, the levels of the T-helper 1 cytokines (interleukin-18 and interferon-gamma) decreased. NP, OP or BP may enhance T-helper 2-type immune responses in NC/Nga mice, which aggravates mite allergen-induced ADSLs. Therefore, the uptake of very low levels of alkylphenols may contribute to the increase in the incidence of atopic dermatitis.
塑料中的邻苯二甲酸酯类物质可作为免疫球蛋白产生的佐剂，从而加重过敏性疾病。然而，烷基酚（用作增塑剂和表面活性剂）对特应性皮炎的影响尚未得到详细研究。因此，本研究的目的是在特应性皮炎小鼠模型中研究烷基酚4-壬基酚（NP）、4-叔辛基酚（OP）和4-叔丁基酚（BP）的作用。对NC/Nga小鼠腹腔注射NP、OP或BP，并在一只耳朵皮下注射螨过敏原以诱导特应性皮炎样皮肤损伤（ADSLs）。观察皮肤状况，并测定血清中的免疫球蛋白水平和损伤部位的炎性细胞因子水平。NP可根据剂量加重螨过敏原诱导的ADSLs。OP和BP也显著加重皮肤损伤，但与剂量无关。烷基酚倾向于增加血清中IgE和抗原特异性IgG1的水平。此外，烷基酚处理可增加损伤部位炎性细胞因子白细胞介素-4和单核细胞趋化蛋白-3的表达。胸腺基质淋巴细胞生成素水平根据ADSL严重程度而增加。相反，辅助性T细胞1细胞因子（白细胞介素-18和干扰素-γ）的水平降低。NP、OP或BP可能增强NC/Nga小鼠的辅助性T细胞2型免疫反应，从而加重螨过敏原诱导的ADSLs。因此，极低水平烷基酚的摄入可能导致特应性皮炎发病率增加。
