Jimenez N, Coll J, Salguero F J, Tafalla C
Centro de Investigación en Sanidad Animal (CISA-INIA), Carretera de Algete a El Casar km. 8,1, Valdeolmos 28130, Madrid, Spain.
Vaccine. 2006 Jul 7;24(27-28):5615-26. doi: 10.1016/j.vaccine.2006.04.061. Epub 2006 May 6.
Since previous results showed that interleukin 8 (IL-8) was induced in rainbow trout (Oncorhynchus mykiss) in response to viral hemorrhagic septicemia virus (VHSV) infection, we have cloned IL-8 in an expression vector (pIL8+) and studied its possible adjuvant effect on the early response to a VHSV immunization model, focusing on the early response of several cytokines induced by a vector coding for the glycoprotein of VHSV (pMCV1.4-G) in the spleen and head kidney. First, we demonstrated that the pIL8+ successfully transcribed IL-8, by induction of IL-8 transcription in the muscle and blood, and by a massive infiltration of neutrophils at the muscle inoculation site. We have studied the effect of pIL8+ co-administration on the expression of two pro-inflammatory cytokines, such as IL-1beta and tumour necrosis factor alpha (TNF-alpha); cytokines that have mainly an inhibitory role, IL-11 and transforming growth factor beta (TGF-beta); and a Th1 type cytokine, IL-18. We demonstrated that the co-administration of pIL8+ with pMCV1.4-G modulates the cytokine response that is induced, mainly by having its effect increasing pro-inflammatory cytokines (IL-1beta and TNF-alpha1), with a greater impact on the spleen, and to a lesser extent in the head kidney. All these data suggest that IL-8 is able to modulate the early cytokine immune response that is produced in response to a DNA vaccine, and therefore, might be a potential immune adjuvant in fish viral vaccination. More work should be done to determine if this modulation has a beneficial effect on protection as seen in other mammal viral models.
由于先前的研究结果表明,虹鳟(Oncorhynchus mykiss)在感染病毒性出血性败血症病毒(VHSV)后会诱导产生白细胞介素8(IL-8),我们已将IL-8克隆到一个表达载体(pIL8+)中,并研究了其对VHSV免疫模型早期反应可能产生的佐剂效应,重点关注编码VHSV糖蛋白的载体(pMCV1.4-G)在脾脏和头肾中诱导的几种细胞因子的早期反应。首先,我们通过在肌肉和血液中诱导IL-8转录,以及在肌肉接种部位出现大量中性粒细胞浸润,证明pIL8+成功转录了IL-8。我们研究了pIL8+共同给药对两种促炎细胞因子(如IL-1β和肿瘤坏死因子α(TNF-α))表达的影响;主要起抑制作用的细胞因子IL-11和转化生长因子β(TGF-β);以及一种Th1型细胞因子IL-18。我们证明,pIL8+与pMCV1.4-G共同给药可调节诱导产生的细胞因子反应,主要是通过增加促炎细胞因子(IL-1β和TNF-α1)的作用来实现,对脾脏的影响更大,对头肾的影响较小。所有这些数据表明,IL-8能够调节针对DNA疫苗产生的早期细胞因子免疫反应,因此,可能是鱼类病毒疫苗接种中的一种潜在免疫佐剂。还需要开展更多工作来确定这种调节是否如在其他哺乳动物病毒模型中所见那样对保护具有有益作用。