Development and validation of a Listeria monocytogenes host resistance model in female Fischer 344 rats.
Meade-BJ; Hayes-BB; Klykken-PC
Toxicol Methods 1998 Mar; 8(1):45-57
The mouse has been used almost exclusively as the experimental animal for host resistance studies in the United States. Host resistance models in mice have been validated and these types of studies are an integral part of the National Toxicology Program's (NTP) immunotoxicology testing program. Given that the Fischer 344 rat is the animal of choice for the NTP's toxicology studies, it was desirable to develop host resistance assays in this rat strain, eliminating the need to extrapolate doses between mouse and rat models. These studies were aimed at the development and the validation of a host resistance model to Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, in the Fischer 344 rat. The results demonstrated that L. monocytogenes infection in the Fischer 344 rat produces a very similar disease with respect to onset and duration as in the mouse. Animals inoculated with up to 3 105 viable colony forming units (CFU) of L. monocytogenes were capable of resisting overt disease when they had an intact immune system. Inoculation of animals with 5 105 cfu resulted in 50% mortality (5/10). However, pretreatment with cyclophosphamide (an immunosuppressive agent) followed by administration of 5 105 L. monocytogenes resulted in 100% mortality. Conversely, pretreatment with Corynebacterium parvum (an immune-enhancing agent) followed by administration of 5 105 L. monocytogenes resulted in 100% survival of animals. Overt disease without recovery was manifested in vehicle-treated animals inoculated with 8 105 and 1 106 microorganism, while earlier deaths and 100% survival resulted after pretreatment with cyclophosphamide or C. parvum , respectively. These data support the use of the inbred Fischer 344 rat for host resistance assays.
Laboratory-animals; Animals; Animal-studies; Models; Diseases; Immune-system-disorders; Mortality-rates
Dr. B. Jean Meade, NIOSH, MS 4020, 1095 Willowdale Road, Morgantown, WV 26505, USA