Miles D W, Happerfield L C, Bobrow L G, Rubens R D
ICRF Clinical Oncology Unit, Guy's Hospital, London, UK.
Histopathology. 1996 Apr;28(4):301-8. doi: 10.1046/j.1365-2559.1996.d01-430.x.
The relevant anti-tumour mechanisms of recombinant interleukin-2 (rIL-2) in vivo are unclear but an influx of T-lymphocytes and macrophages has been noted in regressing lesions. One of the dose limiting toxicities of rIL-2 is the development of a capillary leak syndrome attributed to widespread endothelial activation. Changes in expression of endothelial and leucocyte-associated adhesion molecules were assessed in tumour and uninvolved skin in patients with metastatic breast cancer receiving rIL-2. Increased expression of intracellular adhesion molecule-1, its leucocyte-associated ligand, leucocyte function associated molecule-1, vascular cell adhesion molecule and its ligand, very late after activation antigen-4 as well as members of the selectin family of adhesion molecules, were noted in uninvolved skin following rIL-2. Expression of these adhesion molecules was noted in tumour stroma before rIL-2 but little change was observed following rIL-2 infusion. An influx of monocytes and T-lymphocytes (expressing the IL-2 receptor and of the memory subtype) and a lower number of neutrophils was noted in uninvolved skin following rIL-2. Although monocytes and T-lymphocytes were present in tumour stroma before rIL-2 no changes were observed following infusion. The changes noted in the dermis contrast with those seen at tumour sites and may partly explain the low therapeutic index of rIL-2.
重组白细胞介素-2（rIL-2）在体内的相关抗肿瘤机制尚不清楚，但在消退的病灶中已注意到T淋巴细胞和巨噬细胞的流入。rIL-2的剂量限制性毒性之一是由于广泛的内皮细胞活化导致的毛细血管渗漏综合征。在接受rIL-2的转移性乳腺癌患者的肿瘤和未受累皮肤中评估了内皮细胞和白细胞相关黏附分子表达的变化。在rIL-2治疗后，未受累皮肤中细胞间黏附分子-1、其白细胞相关配体白细胞功能相关分子-1、血管细胞黏附分子及其配体、活化抗原-4以及选择素家族黏附分子成员的表达增加。在rIL-2治疗前，这些黏附分子在肿瘤基质中表达，但在输注rIL-2后观察到变化很小。在rIL-2治疗后，未受累皮肤中出现单核细胞和T淋巴细胞（表达IL-2受体且属于记忆亚型）流入，中性粒细胞数量减少。虽然在rIL-2治疗前肿瘤基质中存在单核细胞和T淋巴细胞，但输注后未观察到变化。真皮中的变化与肿瘤部位的变化形成对比，这可能部分解释了rIL-2治疗指数较低的原因。
