CYTOKINE MESSENGER-RNA LEVELS IN ALOPECIA-AREATA BEFORE AND AFTER TREATMENT WITH THE CONTACT ALLERGEN DIPHENYLCYCLOPROPENONE
CYTOKINE MESSENGER-RNA LEVELS IN ALOPECIA-AREATA BEFORE AND AFTER TREATMENT WITH THE CONTACT ALLERGEN DIPHENYLCYCLOPROPENONE
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DOI：
10.1111/1523-1747.ep12395722
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发表时间：
1994-10-01
影响因子：
6.5
通讯作者：
HAPPLE, R
中科院分区：
文献类型：
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作者：
HOFFMANN, R;WENZEL, E;HAPPLE, R
尽管斑秃 (AA) 中有害信号的性质和解剖目标仍不清楚，但据推测，围绕并浸润毛球的 CD4(+) T 淋巴细胞可能会引发脱发。由于这些 T 淋巴细胞不会促进细胞毒活性，我们推测 AA 是由细胞因子触发的。二苯基环丙烯酮（DCP）的局部免疫治疗是目前最有效的方法。如果 AA 确实是由不同的细胞因子模式产生的，我们可以假设 DCP 的有益作用应该是由接触过敏期间局部分泌的细胞因子介导的。使用半定量逆转录聚合酶链反应，对从 AA 患者在 DCP 成功治疗之前和之后以及健康对照的头皮活检中提取的 RNA 进行半定量逆转录聚合酶链反应，我们检测到在未经治疗的 Totalis 型 AA 中，干扰素 (IFN)-γ、白细胞介素 (IL)-1 β 和 IL-2 的稳态 mRNA 水平增加的 T 细胞反应。 DCP治疗后，IFN-γ表达降低，但仍高于对照组的组成水平，而IL-2、IL-8、IL-10和肿瘤坏死因子-α的mRNA表达增加。我们的结果表明细胞因子参与 AA 的发病机制。未经处理的 AA 中存在 T(H)1 型细胞因子模式，并且这种模式会被 DCP 处理期间分泌的细胞因子所改变。 IL-10 最近被描述为 T(H)1 反应的免疫调节剂，因此，我们假设基底角质形成细胞或病变 T 细胞在 DCP 应用后分泌生物活性 IL-10，从而对病变 T 淋巴细胞产生抑制作用。这一假设可以解释 DCP 的有效性，并暗示局部或病灶内应用重组 IL-10 产生反应的理论可能性。
Although the nature of the noxious signal and the anatomical target in alopecia areata (AA) are still unknown, it has been assumed that CD4(+) T lymphocytes surrounding and infiltrating the hair bulb might trigger the hair loss. As these T lymphocytes do not promote cytotoxic activity we hypothesize that AA is triggered by cytokines. Topical immunotherapy with diphenylcyclopropenone (DCP) is at present the most effective approach. If it is true that AA results from a distinct cytokine pattern, we can hypothesize that the beneficial effect of DCP should be mediated by locally secreted cytokines during the contact allergy. Using semiquantitative reverse transcription-polymerase chain reaction with RNA extracted from scalp biopsies from patients with AA before and after successful treatment with DCP, and from healthy controls we detected a T-cell response with increased steady state mRNA levels for interferon (IFN)-gamma, interleukin (IL)-1 beta, and IL-2 in untreated AA of the totalis type. After DCP treatment, the IFN-gamma expression was reduced but still above the constitutive level found in controls, whereas mRNA expression of IL-2, IL-8, IL-10, and tumor necrosis factor-alpha was increased. Our results point towards cytokines involved in the pathogenesis in AA. A T(H)1 type cytokine pattern is present in untreated AA, and this is modified by cytokines secreted during DCP treatment. IL-10 has recently been described as an immunomodulator of the T(H)1 response and, therefore, we hypothesize that basal keratinocytes or lesional T cells secrete bioactive IL-10 after DCP application, resulting in an inhibitory effect on lesional T lymphocytes. This hypothesis would explain the effectiveness of DCP and implies the theoretical possibility of a response to topical or intralesional application of recombinant IL-10.