Asadullah K, Döcke W D, Haeussler A, Sterry W, Volk H D
Department of Dermatology, University Hospital Charité, Berlin Humboldt University, Germany.
J Invest Dermatol. 1996 Dec;107(6):833-7. doi: 10.1111/1523-1747.ep12330869.
Cytokines are believed to play an important role in the pathogenesis of cutaneous T cell lymphoma. Data regarding the local cytokine pattern in mycosis fungoides (MF) are partly conflicting. Recent studies have suggested a shift from type 1 to type 2 cytokine pattern because IL-4 and IL-5 mRNA have been more frequently detected in lesions of advanced stages. Another study has described a type 1 cytokine pattern in MF lesions. None of the previous studies of cytokine mRNA expression in MF, however, used quantitative methods, and therefore only the presence of a cytokine, but not the level of expression, could be determined. To gain better insight into the development of cytokine pattern during tumor progression we used semiquantitative reverse transcriptase-polymerase chain reaction to analyze cytokine mRNA expression in MF skin lesions at different stages. Biopsies from patients with patch (n = 11), plaque (n = 6), and tumor (n = 3) stage MF were compared with biopsies from patients with pleomorphic T cell lymphoma (n = 5), psoriasis (n = 7), atopic dermatitis (n = 5), and nonlesional skin (n = 8). MF progression was associated with significantly higher IL-10 and lower interferon-gamma mRNA expression. Moreover, the stage-dependent increase in IL-10 mRNA expression was also found in paired samples from individual patients. Unlike in pleomorphic T cell lymphoma, however, typical T helper 2 cells did not seem to be the source of increasing IL-10 in advanced MF, because stage-independent IL-4 mRNA was rarely detected, suggesting contribution of nonlymphoid cells to local IL-10 production. The overexpression of IL-10 in MF may be of importance for tumor progression, because this immunosuppressive cytokine might be involved in downregulation of immunologic tumor surveillance.
细胞因子被认为在皮肤T细胞淋巴瘤的发病机制中起重要作用。关于蕈样肉芽肿(MF)局部细胞因子模式的数据存在部分冲突。最近的研究表明,细胞因子模式从1型向2型转变,因为在晚期病变中更频繁地检测到白细胞介素-4(IL-4)和白细胞介素-5(IL-5)信使核糖核酸(mRNA)。另一项研究描述了MF病变中的1型细胞因子模式。然而,之前关于MF中细胞因子mRNA表达的研究均未使用定量方法,因此只能确定细胞因子的存在,而不能确定其表达水平。为了更好地了解肿瘤进展过程中细胞因子模式的发展,我们使用半定量逆转录聚合酶链反应来分析不同阶段MF皮肤病变中细胞因子mRNA的表达。将斑块期(n = 11)、斑块期(n = 6)和肿瘤期(n = 3)MF患者的活检样本与多形性T细胞淋巴瘤(n = 5)、银屑病(n = 7)、特应性皮炎(n = 5)和非病变皮肤(n = 8)患者的活检样本进行比较。MF的进展与白细胞介素-10(IL-10)显著升高和干扰素-γ(IFN-γ)mRNA表达降低有关。此外,在个体患者的配对样本中也发现了IL-10 mRNA表达的分期依赖性增加。然而,与多形性T细胞淋巴瘤不同,在晚期MF中,典型的辅助性T细胞2型似乎不是IL-10增加的来源,因为很少检测到与分期无关的IL-4 mRNA,这表明非淋巴细胞对局部IL-10的产生有贡献。MF中IL-10的过度表达可能对肿瘤进展很重要,因为这种免疫抑制细胞因子可能参与免疫肿瘤监测的下调。