Ovington K S, Behm C A
Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, Australia.
Mem Inst Oswaldo Cruz. 1997;92 Suppl 2:93-104. doi: 10.1590/s0074-02761997000800013.
In many helminth infected hosts the number of eosinophils increases dramatically, often without any concurrent increases in the number of other leukocytes, so that eosinophils become the dominant cell type. Many experimental investigations have shown that the eosinophilia is induced by interleukin-5 (IL-5) but its functional significance remains unclear. Mice genetically deficient in IL-5 (IL-5-/-) have been used to evaluate the functional consequences of the IL-5 dependent eosinophilia in helminth infected hosts. Host pathology and level of infection were determined in IL-5-/- and wild type mice infected with a range of species representative of each major group of helminths. The effects of IL-5 deficiency were very heterogeneous. Of the six species of helminth examined, IL-5 dependent immune responses had no detectable effect in infections with three species, namely the cestodes Mesocestoides corti and Hymenolepis diminuta and the trematode Fasciola hepatica. In contrast, IL-5 dependent immune responses were functionally important in mice infected with three species, notably all nematodes. Damage to the lungs caused by migrating larvae of Toxocara canis was reduced in IL-5-/- mice. Infections of the intestine by adult stages of either Strongyloides ratti or Heligmosomoides polygyrus were more severe in IL-5-/- mice. Adult intestinal nematodes were clearly deleteriously affected by IL- 5 dependent processes since in its presence there were fewer worms which had reduced fecundity and longevity. The implications of these results for the viability of using inhibitors of IL-5 as a therapy for asthma are considered.
在许多感染蠕虫的宿主体内,嗜酸性粒细胞数量会急剧增加,而其他白细胞数量通常不会同时增加,以至于嗜酸性粒细胞成为主要的细胞类型。许多实验研究表明,嗜酸性粒细胞增多是由白细胞介素-5(IL-5)诱导的,但其功能意义仍不清楚。白细胞介素-5基因缺陷的小鼠(IL-5-/-)已被用于评估在感染蠕虫的宿主体内,依赖IL-5的嗜酸性粒细胞增多所产生的功能后果。在感染了一系列代表各主要蠕虫类群的物种的IL-5-/-小鼠和野生型小鼠中,测定了宿主病理和感染水平。IL-5缺乏的影响非常不一致。在所检测的六种蠕虫中,依赖IL-5的免疫反应在感染三种蠕虫时未产生可检测到的影响,这三种蠕虫分别是绦虫科的中殖孔绦虫和微小膜壳绦虫以及吸虫纲的肝片吸虫。相比之下,依赖IL-5的免疫反应在感染三种蠕虫的小鼠中具有重要功能,特别是所有线虫。犬弓首蛔虫幼虫移行对肺部造成的损伤在IL-5-/-小鼠中有所减轻。在IL-5-/-小鼠中,感染鼠类圆线虫或多房棘球绦虫成虫期对肠道的感染更为严重。成年肠道线虫显然受到依赖IL-5的过程的有害影响,因为在有IL-5的情况下,蠕虫数量减少,繁殖力和寿命降低。本文考虑了这些结果对于使用IL-5抑制剂治疗哮喘的可行性的影响。