Hober D, Ajram L, Chehadeh W, Lazrek M, Goffard A, Dewilde A, Wattré P
Service de virologie, Upres EA3610 CHRU, Lille, France.
Ann Biol Clin (Paris). 2005 Mar-Apr;63(2):155-63.
The potential role of an immune response in HPV-related anogenital disorders had already been anticipated by clinicians. Indeed the lesions efflorescence and the relapsing HPV infection in HIV positive patients as well as the lack of recurrence in patients with spontaneous cure, provided relevant clues for a likely immune mechanism. At present time, the role of the immune system in the development of HPV-related anogenital disorders is well established : HPV induce a humoral and cell mediated immune response. This response is mainly exerted towards infected cells; it is also exerted at the systemic level, through antibodies synthesis, but this pathway remains a secondary one. Due to the limits of the present therapies (either purely destructive and characterized by the rate of recurrences, or antiviral, but difficult to use), it was necessary to find a new treatment type which enhances the local immune response, results in the disappearance of lesions and allows for a decrease in the risk of recurrences. The original mechanism of action of the first cell-mediated immune response modifier: imiquimod, for local use (Aldara 5 % cream) is an answer to this need. The first positive results observed in vitro and in animals were confirmed in patients with HPV anogenital warts in a double blind placebo-controlled study: imiquimod inhibits HPV replication and results in the condyloma regression. Its action is based on the combined activation of the natural local immunity, by stimulating interferon alpha; and of the acquired immunity, by stimulating a T-cell mediated immune response. Thus imiquimod appears to be an original antiviral compound, because it does not act directly on the virus itself.
临床医生早已预见到免疫反应在人乳头瘤病毒(HPV)相关的肛门生殖器疾病中可能发挥的作用。事实上,HIV阳性患者中病变的出现和HPV感染的复发,以及自然治愈患者中无复发情况,都为可能存在的免疫机制提供了相关线索。目前,免疫系统在HPV相关肛门生殖器疾病发展中的作用已得到充分证实:HPV可诱导体液免疫和细胞介导的免疫反应。这种反应主要针对受感染细胞发挥作用;同时也通过抗体合成在全身水平发挥作用,但这条途径是次要的。由于现有治疗方法存在局限性(要么是单纯的破坏性治疗且复发率高,要么是抗病毒治疗但难以应用),因此有必要寻找一种新的治疗方式,这种方式能够增强局部免疫反应,使病变消失,并降低复发风险。首个用于局部治疗的细胞介导免疫反应调节剂咪喹莫特(5%的Aldara乳膏)的原始作用机制就是针对这一需求的解决方案。在体外和动物实验中观察到的首个阳性结果,在一项针对HPV肛门生殖器疣患者的双盲安慰剂对照研究中得到了证实:咪喹莫特可抑制HPV复制并导致尖锐湿疣消退。其作用基于通过刺激α干扰素激活天然局部免疫,以及通过刺激T细胞介导的免疫反应激活获得性免疫的联合作用。因此,咪喹莫特似乎是一种新型抗病毒化合物,因为它并不直接作用于病毒本身。