Narrowband (312-nm) UV-B suppresses interferon gamma and interleukin (IL) 12 and increases IL-4 transcripts: differential regulation of cytokines at the single-cell level.
Narrowband (312-nm) UV-B suppresses interferon gamma and interleukin (IL) 12 and increases IL-4 transcripts: differential regulation of cytokines at the single-cell level.
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DOI：
10.1001/archderm.139.2.155
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发表时间：
2003-02
影响因子：
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通讯作者：
I. Walters;M. Ozawa;I. Cardinale;P. Gilleaudeau;W. Trepicchio;J. Bliss;J. Krueger
中科院分区：
文献类型：
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作者：
I. Walters;M. Ozawa;I. Cardinale;P. Gilleaudeau;W. Trepicchio;J. Bliss;J. Krueger
目的：研究312nm UV-B光疗过程中，是否会改变银屑病病变中残留的活T细胞产生的效应细胞因子和调节细胞因子。前瞻性研究。洛克菲勒大学医院综合临床研究中心。10例难以治疗的中度至重度寻常型牛皮癣成年患者依次纳入我们的研究方案，并在病灶消退后的不同时间点进行活检。窄带（312 nm） UV-B以最低红斑剂量的50%开始，如果没有引起明显的红斑，则每天增加10%至15%。患者继续治疗，直到发现最大的益处。在一些实验中，T细胞用标准TL-01荧光灯泡（Philips Lighting Co, Somerset， NJ）在体外照射。使用流式细胞术进行细胞内细胞因子染色，以量化表皮和外周T细胞中产生细胞因子的细胞的数量。定量逆转录-聚合酶链反应检测白细胞介素（IL） 12、干扰素(IFN) γ、肿瘤坏死因子α、IL-4和IL-10信使RNA的产生。结果：紫外线b治疗可消除银屑病病变中IL-12信使RNA的产生，并使ifn - γ信使RNA的产生降低60%以上（两者均P< 0.03）。在开始UV-B治疗的1至2周内，产生ifn - γ的活T细胞的频率下降了40%至65%。相比之下，在UV-B处理期间，IL-4 mRNA增加了82% (P = 0.05)， 1周后产生IL-4的细胞数量增加了228%。体外实验证实，在单细胞水平上，UV-B对1型T细胞的存活和细胞因子产生有差异调节。结论：治疗性UV-B抑制由IL-12、ifn - γ和IL-8定义的1型（促炎）轴，并可选择性地减少单个T细胞的促炎细胞因子产生。了解UV-B的免疫调节作用将有助于将这种模式整合到基于故意阻断1型t细胞途径中的炎症分子途径的银屑病治疗中。
OBJECTIVE To determine whether 312-nm UV-B alters production of effector and regulatory cytokines by viable T cells that remain in psoriatic lesions during UV-B phototherapy. DESIGN Prospective study. SETTING General clinical research center of The Rockefeller University Hospital. PATIENTS Ten adult patients with moderate to severe psoriasis vulgaris that was difficult to manage were sequentially enrolled in our protocols, and biopsies were taken at various time points from resolving lesions. INTERVENTION Narrowband (312-nm) UV-B was given starting at 50% of a minimum erythema dose, then increased daily 10% to 15% if no apparent erythema was induced. Patients continued with treatment until maximal benefit was noted. In some experiments, T cells were irradiated ex vivo with standard TL-01 fluorescent bulbs (Philips Lighting Co, Somerset, NJ). MAIN OUTCOME MEASURES Intracellular cytokine staining was done using flow cytometry to quantify numbers of cytokine-producing cells from epidermal and peripheral T cells. The production of messenger RNA for interleukin (IL) 12, interferon (IFN) gamma, tumor necrosis factor alpha, IL-4, and IL-10 was measured by quantitative reverse transcription-polymerase chain reaction. RESULTS Ultraviolet-B treatment eliminated production of IL-12 messenger RNA and decreased production of IFN-gamma messenger RNA by more than 60% in irradiated psoriasis lesions (P<.03 for both). Within 1 to 2 weeks of starting UV-B treatment, the frequency of viable T cells producing IFN-gamma decreased 40% to 65%. In contrast, mRNA for IL-4 increased by 82% (P =.05) during UV-B treatment, and the number of IL-4-producing cells increased by 228% after 1 week of treatment. In vitro experiments established that, on the single-cell level, survival and cytokine production by type 1 T cells were differentially regulated by UV-B. CONCLUSIONS Therapeutic UV-B suppresses the type 1 (proinflammatory) axis as defined by IL-12, IFN-gamma, and IL-8, and can selectively reduce proinflammatory cytokine production by individual T cells. Knowledge of the immunomodulatory effects of UV-B will help to integrate this modality in future therapeutics for psoriasis based on deliberate blockade of inflammatory molecular pathways in the type 1 T-cell pathway.