Posadas S J, Leyva L, Torres M J, Rodriguez J L, Bravo I, Rosal M, Fernandez J, Juarez C, Blanca M
Research Unit for Allergic Diseases, Carlos Haya Hospital, Malaga, Spain.
J Allergy Clin Immunol. 2000 Oct;106(4):769-76. doi: 10.1067/mai.2000.109828.
The mechanisms involved in adverse drug reactions with an immunologic basis (ADRIB) can be antibody dependent, mainly IgE or T cell dependent (sensitized T cells). These mechanisms are regulated by a number of cytokines, including IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha, which follow the classical T(H)1/T(H)2 immunologic paradigm. Although evidence for this has been seen in ex vivo studies, the results are heterogeneous, and few in vivo studies have been carried out in subjects with ADRIB.
We studied a group of patients who experienced either immediate reactions (n = 10) or nonimmediate reactions (n = 9) to drugs to determine the cytokine pattern profile during the acute stage of the response, as well as after recovery.
PBMCs were taken at different time intervals of 24 hours or less and 7, 15, and 30 days after the onset of the reaction, and the specific cytokine transcription and production were determined by using quantitative competitive RT-PCR and ELISA, respectively.
There was a transient polarized pattern corresponding to a T(H)1 response with IL-2, IFN-gamma, and TNF-alpha in nonimmediate reactions and to a T(H)2 response with IL-4 in immediate reactions.
This is the first in vivo demonstration of these T(H)1/T(H)2 patterns in subjects with ADRIB and confirms that an immunologic process is occurring related to the mechanisms involved in the pathologic manifestation. These findings are relevant to the understanding of the pathophysiologic mechanisms involved in ADRIB, suggesting that further studies in this direction are warranted.
具有免疫基础的药物不良反应(ADRIB)所涉及的机制可以是抗体依赖性的,主要是IgE或T细胞依赖性的(致敏T细胞)。这些机制受多种细胞因子调节,包括IL-2、IL-4、IL-5、IFN-γ和TNF-α,它们遵循经典的T(H)1/T(H)2免疫模式。尽管在体外研究中已见到相关证据,但结果参差不齐,且针对ADRIB患者的体内研究开展较少。
我们研究了一组对药物发生速发型反应(n = 10)或非速发型反应(n = 9)的患者,以确定反应急性期及恢复后细胞因子模式谱。
在反应发作后24小时或更短时间以及7、15和30天的不同时间间隔采集外周血单核细胞(PBMC),分别使用定量竞争RT-PCR和ELISA测定特定细胞因子的转录和产生情况。
在非速发型反应中出现了对应T(H)1反应的瞬时极化模式,伴有IL-2、IFN-γ和TNF-α;在速发型反应中出现了对应T(H)2反应的瞬时极化模式,伴有IL-4。
这是首次在ADRIB患者体内证实这些T(H)1/T(H)2模式,并证实与病理表现所涉及机制相关的免疫过程正在发生。这些发现对于理解ADRIB所涉及的病理生理机制具有重要意义,表明有必要在这个方向上进一步开展研究。