Brunner H
Bayer AG, Pharma Research Center, Wuppertal, Federal Republic of Germany.
Wien Klin Wochenschr. 1997 Aug 8;109(14-15):569-73.
Animal models for the study of human diseases must be replaced by in vitro methods, whenever possible. However, when critically evaluated, they remain indispensable for the solution of some specific problems in infectious diseases. These include the pathogenesis, the host response, as well as the study of antimicrobial agents and vaccines. Under these conditions animal models, which closely reflect the situation in man, are especially valuable. Two models may serve as "ideal" examples for the study of human diseases: firstly mouse typhoid for the study of systemic infections with Salmonella typhimurium. This model has been employed for many decades to examine various aspects of human typhoid fever. A second model is the experimental infection of hamsters with Mycoplasma pneumoniae as a model of local infection in the respiratory tract. Mycoplasma and ureaplasma infections of man are frequent, but rarely life threatening. Chick embryos, rats, hamsters, guinea pigs, and monkeys (rhesus monkeys and chimpanzees) are susceptible to experimental infection with M. pneumoniae. Some mouse strains are also colonized with M. pneumoniae after intranasal inoculation, but histopathological alterations similar to the hamster model have not been established in a reproducible way in mice. Hamsters have, therefore, been important for the evaluation of antibiotics and vaccines. Local immunity in the respiratory tract, the possible contribution of the immune response to disease pathogenesis, persistence of the organisms in the respiratory tract after clinical symptoms are cured by antibiotic therapy, and the role of cytokines in protection or disease pathogenesis remain interesting areas for future research, which could be addressed in animal models. The evaluation of the role of mycoplasmas and ureaplasmas in genital tract infections is by far more complex and even more difficult in AIDS and rheumatoid arthritis, because several species of mycoplasmas and Ureaplasma urealyticum can be isolated from a large proportion of healthy individuals. Furthermore, good models for the study of these infections are not available.
只要有可能,用于人类疾病研究的动物模型必须被体外方法所取代。然而,经过严格评估后发现,在解决传染病的某些特定问题时,动物模型仍然不可或缺。这些问题包括发病机制、宿主反应,以及抗菌药物和疫苗的研究。在这些情况下,能紧密反映人类情况的动物模型尤其有价值。有两种模型可作为研究人类疾病的“理想”范例:其一,小鼠伤寒模型用于研究鼠伤寒沙门氏菌的全身感染。该模型已被使用数十年,用于研究人类伤寒热的各个方面。第二个模型是将肺炎支原体实验性感染仓鼠,作为呼吸道局部感染的模型。人类支原体和脲原体感染很常见,但很少危及生命。鸡胚、大鼠、仓鼠、豚鼠和猴子(恒河猴和黑猩猩)对肺炎支原体的实验性感染易感。一些小鼠品系经鼻内接种后也会被肺炎支原体定植,但尚未以可重复的方式在小鼠中建立与仓鼠模型相似的组织病理学改变。因此,仓鼠对于评估抗生素和疫苗很重要。呼吸道局部免疫、免疫反应对疾病发病机制的可能作用、抗生素治疗使临床症状治愈后病原体在呼吸道中的持续存在,以及细胞因子在保护或疾病发病机制中的作用,仍然是未来研究中有趣的领域,可在动物模型中进行探讨。评估支原体和脲原体在生殖道感染中的作用要复杂得多,在艾滋病和类风湿性关节炎中更是困难,因为从很大比例的健康个体中都能分离出几种支原体和溶脲脲原体。此外,目前还没有用于研究这些感染的良好模型。