Bessis N, Fradelizi D, Fournier C, Boissier M C
INSERM U283, Hôpital Cochin, Université René-Descartes, Paris.
C R Seances Soc Biol Fil. 1995;189(4):579-90.
Cytokines may exert anti-inflammatory properties, allowing the hypothesis of their potential therapeutic use. Targeting the cytokines balance may modify the course of subsequent inflammatory events in an autoimmune disease. Many data are available. Interferon-gamma can be blocked by an anti-interferon-gamma monoclonal antibody: if the treatment is administered in the early phase of an autoimmune disease such as collagen-induced arthritis, the course of the disease is worsened; if the treatment is given later, the disease can be improved; these results are mirrored by treatment with high doses of the cytokine itself. Pharmacologic effects of antiinflammatory cytokines such as interleukin (IL)-4, IL-10 or IL-13 are a protection against several experimental autoimmune diseases. The very short half-life of cytokines makes them difficult and expensive to use directly; in such occurrence, high quantities have to be frequently injected. In this context, gene therapy appears as an effective alternative solution: the transfection of cells with cytokines genes (e.g. either IL-4 or IL-13) then the engraftment of these vectors in animals, permit the in vivo secretion of high levels of cytokines, and result in the protection of the animals from the development of the disease.
细胞因子可能具有抗炎特性,这使得它们具有潜在治疗用途的假说成立。针对细胞因子平衡可能会改变自身免疫性疾病后续炎症事件的进程。已有许多相关数据。干扰素-γ可被抗干扰素-γ单克隆抗体阻断:如果在自身免疫性疾病(如胶原诱导性关节炎)的早期给予该治疗,疾病进程会恶化;如果在后期给予治疗,疾病则可得到改善;高剂量细胞因子本身的治疗也会出现类似结果。抗炎细胞因子如白细胞介素(IL)-4、IL-10或IL-13的药理作用是对几种实验性自身免疫性疾病具有保护作用。细胞因子的半衰期非常短,这使得它们直接使用困难且成本高昂;在这种情况下,必须频繁注射大量细胞因子。在此背景下,基因治疗似乎是一种有效的替代解决方案:用细胞因子基因(如IL-4或IL-13)转染细胞,然后将这些载体植入动物体内,可使动物体内高水平分泌细胞因子,并保护动物不发生疾病。