Posadas Sinforiano J, Torres María J, Mayorga Cristobalina, Juarez Carlos, Blanca Miguel
Allergy Service, La Paz Hospital, Madrid, Spain.
Blood Cells Mol Dis. 2002 Sep-Oct;29(2):179-89. doi: 10.1006/bcmd.2002.0555.
Drugs can induce IgE mediated or T cell dependent immunological reactions. T cell dependent reactions are poorly understood, although T lymphocytes have been proposed as a protagonist in a number of non-immediate immunological reactions (NIR). The objective was to study in vivo different regulatory and proinflammatory cytokines and cytotoxic markers in patients with NIR to drugs. Twenty patients with NIR after drug intake were classified into two groups: Group A (severe), Stevens-Johnson syndrome and toxic epidermal necrolysis; and Group B (mild), maculopapular exanthema and desquamative exanthema. Another 25 subjects taking the same drugs but without reactions formed a control group. Samples were obtained within 24 hours of the reaction and 30 days later. IL-2, IL-4, IFN, TNF, perforin, granzyme B (GrB), and FasL mRNA expression levels were determined in peripheral blood mononuclear cells by competitive RT-PCR. There were 9 patients in Group A and 11 in Group B. The drugs involved were betalactams (8), anticonvulsants (6), allopurinol (1), sulfamethoxazole (1), amiodarone (1) dypirone (2), and erythromicine+paracetamol (1). At the acute stage there was a high increase of IL-2, IFN, and TNF mRNA expression in both groups vs. controls, perforin and GrB varied in each group with patients in Group A having the highest values, and FasL was only expressed in Group A. Relationships between the cytokines were only significant in Group B (p < 0.05). Only the relation between IFN-gamma and TNF-alpha was significant in Group A. There was a significant correlation between cytotoxic markers in both groups (A: p < 0.001, B: p < 0.01). These data demonstrate the complexity of the Th1 phenotype in NIR after drug intake. In patients with mild NIR, cytokines appear to play a closely related role, whereas cytotoxic markers appear more relevant in severe reactions.
药物可诱发IgE介导或T细胞依赖性免疫反应。尽管T淋巴细胞已被认为是许多非即时免疫反应（NIR）中的主角，但对T细胞依赖性反应的了解仍很少。目的是研究药物性NIR患者体内不同的调节性和促炎性细胞因子以及细胞毒性标志物。20例药物摄入后发生NIR的患者分为两组：A组（重度），史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症；B组（轻度），斑丘疹和脱屑性皮疹。另外25名服用相同药物但无反应的受试者组成对照组。在反应发生后24小时内和30天后采集样本。通过竞争性逆转录-聚合酶链反应（RT-PCR）测定外周血单个核细胞中白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、干扰素（IFN）、肿瘤坏死因子（TNF）、穿孔素、颗粒酶B（GrB）和FasL的信使核糖核酸（mRNA）表达水平。A组9例，B组11例。涉及的药物有β-内酰胺类（8种）、抗惊厥药（6种）、别嘌醇（1种）、磺胺甲恶唑（1种）、胺碘酮（1种）、安乃近（2种）以及红霉素+对乙酰氨基酚（1种）。在急性期，两组与对照组相比，IL-2、IFN和TNF的mRNA表达均显著升高，穿孔素和GrB在每组中各不相同，A组患者的值最高，FasL仅在A组中表达。细胞因子之间的关系仅在B组中有显著性（p<0.05）。在A组中，仅干扰素-γ与肿瘤坏死因子-α之间的关系有显著性。两组中细胞毒性标志物之间存在显著相关性（A组：p<0.001，B组：p<0.01）。这些数据表明药物摄入后NIR中Th1表型的复杂性。在轻度NIR患者中，细胞因子似乎发挥密切相关的作用，而细胞毒性标志物在重度反应中似乎更相关。
