Carter Quincy L, Curiel Rafael E
Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN, USA.
Vet Immunol Immunopathol. 2005 Aug 15;107(1-2):105-18. doi: 10.1016/j.vetimm.2005.04.003.
Porcine respiratory and reproductive syndrome virus (PRRSV) disease, one of the most economically significant viral diseases in the swine industry, is characterized by miscarriages, premature farrowing, stillborn pigs, and respiratory disease associated with death and chronic poor performance of nursing and weaned pigs. Interleukin-12 (IL-12) is a key component in driving the development of cell-mediated immunity as well as stimulating interferon-gamma (IFN-gamma) production from T cells and natural killer cells. Although some studies have investigated the use of IL-12 as a vaccine adjuvant in swine, little is known about its effectiveness as a treatment against viral diseases in swine. The present study investigated whether recombinant porcine IL-12 (rpIL-12) enhances the immune response and thereby diminishes the effects of PRRSV infection in young pigs. Interestingly, in vitro experiments demonstrated that rpIL-12 is capable of inducing swine pulmonary alveolar macrophages (PAMs), the target cells of PRRSV, to produce IFN-gamma in a dose and time dependent manner. In addition, in vitro studies also revealed that rpIL-12 treatment was capable of significantly reducing PRRSV viral titers in PAMs. In vivo administration of rpIL-12 significantly decreased PRRSV titers in the lungs and blood of infected animals. Furthermore, treatment with rpIL-12 prevented significant growth retardation in PRRSV-infected animals. Finally, in response to viral antigen recall challenge, PAMs isolated from rpIL-12-treated/PRRSV-infected animals produced greater amounts of IFN-gamma and lesser amounts of interleukin-10 than PAMs isolated from non-rpIL-12-treated/PRRSV-infected animals. Taken together our data indicate that treatment with rpIL-12 may provide an effective approach to control or ameliorate PRRSV-induced disease in swine.
猪繁殖与呼吸综合征病毒(PRRSV)病是养猪业中最具经济影响力的病毒性疾病之一,其特征为流产、早产、死胎以及与哺乳仔猪和断奶仔猪死亡及慢性生长不良相关的呼吸道疾病。白细胞介素-12(IL-12)是驱动细胞介导免疫发展以及刺激T细胞和自然杀伤细胞产生γ干扰素(IFN-γ)的关键成分。尽管一些研究调查了IL-12作为猪疫苗佐剂的用途,但对于其作为猪病毒性疾病治疗药物的有效性知之甚少。本研究调查了重组猪IL-12(rpIL-12)是否能增强免疫反应,从而减轻PRRSV感染对仔猪的影响。有趣的是,体外实验表明,rpIL-12能够以剂量和时间依赖性方式诱导PRRSV的靶细胞——猪肺泡巨噬细胞(PAM)产生IFN-γ。此外,体外研究还表明,rpIL-12处理能够显著降低PAM中的PRRSV病毒滴度。rpIL-12的体内给药显著降低了感染动物肺部和血液中的PRRSV滴度。此外,rpIL-12处理可防止PRRSV感染动物出现明显的生长迟缓。最后,在对病毒抗原回忆攻击的反应中,从经rpIL-12处理/PRRSV感染动物分离的PAM比从未经rpIL-12处理/PRRSV感染动物分离的PAM产生更多的IFN-γ和更少的白细胞介素-10。综合来看,我们的数据表明,rpIL-12处理可能为控制或改善猪PRRSV诱导的疾病提供一种有效方法。