Di Renzo M, Rubegni P, Pasqui A L, Pompella G, De Aloe G, Sbano P, Cuccia A, Castagnini C, Auteri A, Laghi Pasini F, Fimiani M
Department of Internal Medicine and Immunology, University of Siena, 53100 Siena, Italy.
Br J Dermatol. 2005 Jul;153(1):59-65. doi: 10.1111/j.1365-2133.2005.06482.x.
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear.
To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production.
We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient.
ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated.
These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.
慢性移植物抗宿主病(cGVHD)是异基因骨髓移植的主要并发症。体外光化学疗法(ECP)最近已被引入作为对传统免疫抑制治疗难治的cGVHD病例的替代治疗方法,但其作用机制尚不清楚。
在7例cGVHD患者中研究ECP对单核细胞凋亡抗性和单核细胞细胞因子产生的影响。
我们设计了一个体外模型,该模型可以模拟经ECP处理的外周血单个核细胞再输注的潜在体内效应。该模型基于将经ECP处理的淋巴细胞与来自同一患者的未处理单核细胞共培养。
ECP未加速单核细胞的自发凋亡。然而,经ECP处理的单核细胞产生的白细胞介素(IL)-12量增加。相比之下,共培养中单核细胞的IL-12产生未增加,但IL-10产生上调。
这些结果表明,大量自体凋亡淋巴细胞的再输注通过上调作为免疫抑制细胞因子的IL-10对ECP的治疗结果具有重要意义。