Bocci V, Pessina G P, Paulesu L, Nicoletti C
Institute of General Physiology, University of Siena, Italy.
J Biol Response Mod. 1988 Aug;7(4):390-400.
Human recombinant (R) interferon-alpha 2 (either cold or labeled with 125I or 131I) has been administered through different routes [intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.)] and its distribution in lymph and plasma has been evaluated in rabbits and pigs. After i.v. (bolus) administration, the lymph/plasma ratio was about 1. After s.c. and i.m. administration, the ratio varied from an average of 0.8 up to 2, respectively, indicating that R interferon-alpha 2 is preferentially absorbed via lymphatics when injected into the shank muscles. Another novel result is that the ratio is markedly increased after s.c. administration of interferon-alpha 2 with a solution containing 12.5% human albumin. In this case, albumin acts as an interstitial fluid expander, thereby increasing the fluid pressure and favoring lymphatic absorption. Similar results were obtained using either cold or labeled interferons in rabbits; moreover, the effect of albumin was confirmed in the pig by simultaneously injecting 131I-interferon (in saline) and 125I-interferon (in albumin solution) in the left and right subcutis of the shanks, respectively. All of these data suggest that the indirect lymphatic route is a feasible proposition, and that by modifying the absorption, the distribution and fate of interferon may improve the therapeutic index of biological response modifiers.
人重组（R）干扰素-α2（未标记或用125I或131I标记）已通过不同途径给药[静脉内（i.v.）、肌肉内（i.m.）和皮下（s.c.）]，并在兔和猪体内评估了其在淋巴液和血浆中的分布情况。静脉推注给药后，淋巴液/血浆比值约为1。皮下和肌肉内给药后，该比值分别从平均0.8变化到2，这表明当将R干扰素-α2注射到小腿肌肉中时，它优先通过淋巴管吸收。另一个新的结果是，皮下注射含12.5%人白蛋白的溶液后，干扰素-α2的该比值显著增加。在这种情况下，白蛋白起到组织间液扩容剂的作用，从而增加流体压力并有利于淋巴吸收。在兔中使用未标记或标记的干扰素均获得了类似结果；此外，通过分别在小腿左右两侧皮下同时注射131I-干扰素（生理盐水溶液）和125I-干扰素（白蛋白溶液），在猪中证实了白蛋白的作用。所有这些数据表明，间接淋巴途径是一个可行的方案，并且通过改变干扰素的吸收、分布和转归可能会提高生物反应调节剂的治疗指数。
