Bocci V
Institute of General Physiology and Nutritional Sciences, Faculty of Pharmacy, University of Siena, Italy.
Crit Rev Ther Drug Carrier Syst. 1992;9(2):91-133.
Interferons (IFNs) are a complex group of proteins and glycoproteins able to express antiviral, immunomodulatory, and differentiation activities. In physiological conditions, they are produced upon induction, in basal amounts, and in restricted microenvironments where they act in a paracrine fashion, hardly reaching the circulation and not affecting parenchymal cells. In some acute infections, production of IFN is diffused and, therefore, IFN levels become detectable in plasma, and side effects, such as the typical flu-like syndrome, ensue. A similar situation occurs during pharmacological therapy, particularly when IFN is administered through conventional routes (IV, IM, and SC). We have finally realized that IFNs are normally not circulatory proteins, and because they are unselective during therapeutic intervention, toxicity can overcome beneficial effects. For this reason, there is a pressing need to optimize treatment, dosages, and schedules for improving the therapeutic index. A further important issue is the definition of routes of IFN administration able to achieve the maximal activity where needed, and in fact, when IFNs are used as cytostatic drugs, regional therapy improves the treatment. However, when IFNs are used as immunomodulatory agents, other strategies must be sought, and the interaction of IFN with epithelial membranes and mucosal associated lymphoid tissue becomes important. Hence, delivery via oropharyngeal, intestinal, rectal, bronchioalveolar, and lymphatic routes appears useful probably because they simulate the physiological distribution and action of IFNs.
干扰素（IFN）是一组复杂的蛋白质和糖蛋白，具有抗病毒、免疫调节和分化活性。在生理条件下，它们在诱导后以基础量在受限的微环境中产生，以旁分泌方式发挥作用，很少进入循环且不影响实质细胞。在一些急性感染中，IFN的产生广泛存在，因此血浆中可检测到IFN水平，并随之出现诸如典型的流感样综合征等副作用。在药物治疗期间也会出现类似情况，尤其是当通过传统途径（静脉内、肌内和皮下）给予IFN时。我们最终认识到，IFN通常不是循环蛋白，并且由于它们在治疗干预期间没有选择性，毒性可能会超过有益效果。因此，迫切需要优化治疗方法、剂量和给药方案以提高治疗指数。另一个重要问题是确定能够在需要的部位实现最大活性的IFN给药途径，事实上，当IFN用作细胞毒性药物时，区域治疗可改善治疗效果。然而，当IFN用作免疫调节剂时，必须寻求其他策略，并且IFN与上皮膜和黏膜相关淋巴组织的相互作用变得很重要。因此，通过口咽、肠道、直肠、支气管肺泡和淋巴途径给药似乎是有用的，这可能是因为它们模拟了IFN的生理分布和作用。
