Kaufman H L, Rao J B, Irvine K R, Bronte V, Rosenberg S A, Restifo N P
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Immunother. 1999 Nov;22(6):489-96. doi: 10.1097/00002371-199911000-00003.
Interleukin-10 (IL-10) has a wide range of in vivo biological activities and is a key regulatory cytokine of immune-mediated inflammation. The authors found that murine IL-10 given 12 hours after a recombinant vaccinia virus (rVV) containing the LacZ gene significantly enhanced the treatment of mice bearing 3-day-old pulmonary metastases expressing beta-galactosidase. Because IL-10 has been shown to inhibit the functions of key elements of both innate and acquired immune responses, the authors hypothesized that IL-10 might act by inhibiting clearance of the rVV, thus prolonging exposure to the experimental antigen. However, evidence that IL-10 was not acting primarily through such negative regulatory mechanisms included the following: (a) IL-10 also enhanced the therapeutic effectiveness of a recombinant fowlpox virus, which cannot replicate in mammalian cells; (b) Titers of rVV in immunized mice were lower, not higher; and (c) Although IL-10 did not alter levels of anti-vaccinia anti-bodies or natural killer cell activity, rVV-primed mice treated with IL-10 had enhanced vaccinia-specific cytotoxic T-lymphocyte activity. Thus, IL-10 enhanced the function of a recombinant poxvirus-based anti-cancer vaccine and may represent a potential adjuvant in the vaccination against human cancers using recombinant poxvirus-based vaccines.
白细胞介素-10（IL-10）具有广泛的体内生物学活性，是免疫介导炎症的关键调节细胞因子。作者发现，在含有LacZ基因的重组痘苗病毒（rVV）感染12小时后给予小鼠IL-10，可显著增强对携带表达β-半乳糖苷酶的3日龄肺转移瘤小鼠的治疗效果。由于IL-10已被证明可抑制先天性和获得性免疫反应关键成分的功能，作者推测IL-10可能通过抑制rVV的清除起作用，从而延长对实验性抗原的暴露时间。然而，IL-10并非主要通过这种负调节机制起作用的证据包括：（a）IL-10还增强了重组鸡痘病毒的治疗效果，而该病毒无法在哺乳动物细胞中复制；（b）免疫小鼠体内rVV的滴度较低，而非较高；（c）虽然IL-10未改变抗痘苗抗体水平或自然杀伤细胞活性，但用IL-10处理的经rVV致敏的小鼠具有增强的痘苗特异性细胞毒性T淋巴细胞活性。因此，IL-10增强了基于重组痘病毒的抗癌疫苗的功能，可能代表使用基于重组痘病毒的疫苗预防人类癌症的潜在佐剂。
