Emmanouilides C E, Luo J, Baldwin G, Buckley D, Lau P, Lopez E, Tabibzadeh S, Yu J, Wolin M, Rigor R, Territo M, Black A C
UCLA School of Medicine, Division of Medicine 90095, USA.
Bone Marrow Transplant. 1996 Aug;18(2):369-75.
Graft-versus-host disease (GVHD) is a serious complication following allogeneic bone marrow transplantation (BMT). Initial immunologic events that are thought to lead to clinical GVHD include allogeneic antigen presentation, CD4+ T cell proliferation and eventually generation of specific cytotoxic lymphocytes. Interleukin-10 (IL-10) has been shown to inhibit the function of antigen presenting cells (APC) and to reduce lymphocyte proliferation. In this study we investigated the possible role of recombinant murine IL-10 (rmIL-10) as prophylactic treatment of GVHD in a murine BMT model involving B10.BR donor mice (H-2k) and AKR recipients (H-2k). In particular, we wished to determine whether early post-BMT administration of IL-10 would suppress GVHD by interfering with macrophage function and inflammatory cytokine production during the proposed "afferent' phase of GVHD. In MLR assays, rmIL-10 significantly inhibited the proliferation of donor spleen cells when stimulated by irradiated recipient spleen cells in a dose-dependent manner. In murine BMT, rmIL-10 was administered exogenously by intraperitoneal injection of 100 U daily in two different dosage schedules, on days-1, 0, 1, 2, 3, 6 to target the early post-BMT phase, and days-1, 0, 3, 5, 7, 10 after BMT, to administer the same total dose throughout the engraftment period. IL-10 injected mice had lower plasma IL-1 alpha levels on day 3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), suggesting that both macrophage function and inflammatory cytokine production were inhibited. In contrast to the MLR data, no significant improvement in morbidity and mortality from GVHD was observed. Therefore, IL-10 does not appear to be useful in GVHD prophylaxis.
移植物抗宿主病（GVHD）是异基因骨髓移植（BMT）后的一种严重并发症。被认为会导致临床GVHD的初始免疫事件包括异基因抗原呈递、CD4 + T细胞增殖以及最终产生特异性细胞毒性淋巴细胞。白细胞介素-10（IL-10）已被证明可抑制抗原呈递细胞（APC）的功能并减少淋巴细胞增殖。在本研究中，我们在一个涉及B10.BR供体小鼠（H-2k）和AKR受体（H-2k）的小鼠BMT模型中，研究了重组鼠IL-10（rmIL-10）作为GVHD预防性治疗的可能作用。特别地，我们希望确定在BMT后早期给予IL-10是否会通过在GVHD的所谓“传入”阶段干扰巨噬细胞功能和炎性细胞因子产生来抑制GVHD。在混合淋巴细胞反应（MLR）试验中，rmIL-10以剂量依赖的方式显著抑制了受照射的受体脾细胞刺激时供体脾细胞的增殖。在小鼠BMT中，通过两种不同的给药方案每天腹腔注射100 U外源性给予rmIL-10，一种方案是在-1、0、1、2、3、6天给药，以针对BMT后的早期阶段，另一种方案是在BMT后的-1、0、3、5、7、10天给药，以便在整个植入期给予相同的总剂量。注射IL-10的小鼠在第3天血浆IL-1α水平较低（12 pg/ml，而对照组为64 pg/ml，P < 0.05），这表明巨噬细胞功能和炎性细胞因子产生均受到抑制。与MLR数据相反，未观察到GVHD的发病率和死亡率有显著改善。因此，IL-10似乎对GVHD预防无用。
