Lampson G P, Field A K, Tytell A A, Hilleman M R
J Interferon Res. 1981;1(4):539-49. doi: 10.1089/jir.1981.1.539.
A soluble complex of poly I:C and poly-L-lysine (poly I:C/poly-L-lysine) has been prepared that induces high titers of circulating interferon in monkeys. By limiting the molar ratio of lysine to nucleotide to 0.5, a complex was formed that was soluble up to 2.0 mg poly I:C/ml of phosphate-buffered saline. Complexes of poly I:C with poly-L-lysine of various molecular weights, and in a constant ratio (0.5) of lysine to nucleotide, were evaluated for capacity to induce serum interferon in grivet monkeys. Substantial enhancement (10- to 100-fold) of the capacity of poly I:C to induce interferon in grivet monkeys was observed using poly I:C complexed with poly-L-lysines of molecular weight 10(4) daltons or greater. The poly I:C/poly-L-lysine as an effective inducer of interferon in grivet monkeys, rhesus monkeys, chimpanzees and marmosets. A high interferon titer (greater than 100 units/ml blood) was maintained in grivet monkeys by repeated daily administration of the complex. No long-term hyporesponsiveness was noted following repeat inductions over a period of months. The serum interferon produced in monkeys in response to poly I:C/poly-L-lysine resembled human leukocyte interferon in its biological characteristics.
已制备出聚肌胞苷酸与聚-L-赖氨酸的可溶性复合物(聚肌胞苷酸/聚-L-赖氨酸),其可在猴体内诱导产生高滴度的循环干扰素。通过将赖氨酸与核苷酸的摩尔比限制为0.5,形成了一种在高达2.0毫克聚肌胞苷酸/毫升磷酸盐缓冲盐水中均可溶解的复合物。对不同分子量且赖氨酸与核苷酸比例恒定(0.5)的聚肌胞苷酸与聚-L-赖氨酸的复合物,评估其在绿猴体内诱导血清干扰素的能力。当使用与分子量为10(4)道尔顿或更大的聚-L-赖氨酸复合的聚肌胞苷酸时,观察到聚肌胞苷酸在绿猴体内诱导干扰素的能力有显著增强(10至100倍)。聚肌胞苷酸/聚-L-赖氨酸可作为绿猴、恒河猴、黑猩猩和狨猴体内干扰素的有效诱导剂。通过每日重复给药该复合物,绿猴体内可维持高干扰素滴度(大于100单位/毫升血液)。在数月的重复诱导后,未观察到长期低反应性。猴体内因聚肌胞苷酸/聚-L-赖氨酸产生的血清干扰素在生物学特性上类似于人白细胞干扰素。