Dennert G, Lotan R
Eur J Immunol. 1978 Jan;8(1):23-9. doi: 10.1002/eji.1830080106.
Retinoic acid (RA), a vitamin A derivative with anti-tumor activity, was assayed for its effects on the immune system in mice. High doses of this compound (1000 microgram/mouse/day) have toxic effects and cause depletion on the peripheral lymphoid organs (spleen, thymus) while leaving the bone marrow cells unaffected. Both the in vivo and in vitro induction of cell-mediated cytotoxicity (CMC) to allogeneic tumor cells is stimulated at least tenfold by low doses (25--300 microgram/mouse/day) of RA while high doses suppress CMC induction. RA is shown to be a specific adjuvant for the induction of cytotoxic thymus-derived lymphocytes (T cells) and not a general T cell mitogen or adjuvant. It does not enhance the proliferative response in the mixed lymphocyte culture nor does it stimulate lymphocyte proliferation in response to the mitogens concanavalin A and phytohemagglutinin. The induction of cooperating T cells and the delayed-type hypersensitivity reaction are also not stimulated by RA. In contrast to the reported stimulatory effects of retinyl palmitate and retinyl acetate, RA does not stimulate the humoral response to erythrocytes. The strong adjuvant effects that RA has on the induction of CMC at low doses may be responsible for its anti-tumor activity.
维甲酸（RA）是一种具有抗肿瘤活性的维生素A衍生物，已对其在小鼠免疫系统中的作用进行了测定。高剂量的这种化合物（1000微克/小鼠/天）具有毒性作用，会导致外周淋巴器官（脾脏、胸腺）耗竭，而骨髓细胞不受影响。低剂量（25 - 300微克/小鼠/天）的RA能将对同种异体肿瘤细胞的细胞介导细胞毒性（CMC）的体内和体外诱导至少提高10倍，而高剂量则抑制CMC诱导。RA被证明是诱导细胞毒性胸腺来源淋巴细胞（T细胞）的特异性佐剂，而不是一般的T细胞丝裂原或佐剂。它既不增强混合淋巴细胞培养中的增殖反应，也不刺激淋巴细胞对促有丝分裂剂刀豆球蛋白A和植物血凝素的增殖。RA也不刺激协同T细胞的诱导和迟发型超敏反应。与报道的棕榈酸视黄酯和醋酸视黄酯的刺激作用相反，RA不刺激对红细胞的体液反应。低剂量的RA对CMC诱导具有的强大佐剂作用可能是其抗肿瘤活性的原因。
