Washburn W K, Otsu I, Gottschalk R, Monaco A P
Division of Organ Transplantation, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Surg Res. 1996 May;62(2):179-83. doi: 10.1006/jsre.1996.0192.
PGG-glucan is an immunomodulator which can enhance the host response to infection. Phase I/II clinical trials have documented the safety and potential efficacy of this compound to reduce postoperative infectious complications in high risk surgical patients. Organ transplant recipients may benefit from this drug due to their high rates of postoperative infectious complications. A rat cardiac rejection model (ACI --> Lew) and a mouse skin graft model (C3H/HeJ --> B6AF1/J) were used with four treatment arms (control, Cyclosporine A (CsA), antilymphocyte serum (ALS), and CsA + ALS with and without PGG-glucan). Small intestinal allografts (Lew --> LBNF1) were performed in rats to evaluate GVHD. In the mouse GVHD model, donor splenocytes were given to irradiated recipients (C57BL/6 --> B6AF1), with and without PGG-glucan treatment. There was no difference in survival between PGG-glucan treatment and placebo for the control, CsA, and CsA + ALS groups in rat cardiac recipients. Recipients receiving ALS and treated with PGG-glucan survived a median of 42.5 days versus 63.5 days for those ALS-treated animals not receiving PGG-glucan (P = 0.045). In the remaining groups there was no difference in survival between PGG-glucan-treated groups and the control groups. PGG-glucan did not shorten survival in three of four treatment groups in the rat cardiac rejection model. High dose ALS with PGG-glucan did result in a marginal decrease in survival in cardiac allograft recipients. If the one outlying animal with indefinite survival is excluded, the difference is not statistically significant (P = 0.098). These results show that even though PGG-glucan has immunostimulatory properties, it does not significantly potentiate rejection or GVHD in these animal models. This preliminary work may be important in determining whether PGG-glucan can be safely given to immunosuppressed organ transplant recipients to reduce postoperative infectious complications.
PGG-葡聚糖是一种免疫调节剂，可增强宿主对感染的反应。I/II期临床试验已证明该化合物在降低高危手术患者术后感染并发症方面的安全性和潜在疗效。器官移植受者术后感染并发症发生率较高，可能会从这种药物中获益。使用大鼠心脏排斥模型（ACI→Lew）和小鼠皮肤移植模型（C3H/HeJ→B6AF1/J），设置四个治疗组（对照组、环孢素A（CsA）、抗淋巴细胞血清（ALS）以及使用和不使用PGG-葡聚糖的CsA + ALS组）。在大鼠中进行小肠同种异体移植（Lew→LBNF1）以评估移植物抗宿主病（GVHD）。在小鼠GVHD模型中，给经照射的受体（C57BL/6→B6AF1）输注供体脾细胞，同时进行和不进行PGG-葡聚糖治疗。在大鼠心脏移植受体中，PGG-葡聚糖治疗组与对照组、CsA组和CsA + ALS组的安慰剂组在生存率上没有差异。接受ALS并接受PGG-葡聚糖治疗的受体中位生存期为42.5天，而未接受PGG-葡聚糖治疗的ALS治疗动物中位生存期为63.5天（P = 0.045）。在其余组中，PGG-葡聚糖治疗组与对照组在生存率上没有差异。在大鼠心脏排斥模型的四个治疗组中，有三个组PGG-葡聚糖并未缩短生存期。高剂量ALS联合PGG-葡聚糖确实导致心脏同种异体移植受体的生存期略有下降。如果排除一只生存期不确定的异常动物，差异无统计学意义（P = 0.098）。这些结果表明，尽管PGG-葡聚糖具有免疫刺激特性，但在这些动物模型中它并未显著增强排斥反应或GVHD。这项初步工作对于确定PGG-葡聚糖是否可以安全地给予免疫抑制的器官移植受者以减少术后感染并发症可能具有重要意义。
