An LPS based method to stimulate the inflammatory response in growing rabbits

Abstract

[EN] Reliable indicators are needed to study the relationship between the inflammatory response of the growing rabbit and breeding factors such as feeding practices. A lipopolysaccharide (LPS) stimulation of the inflammatory response is a valid model of bacterial infection in laboratory animals, but no data on the growing rabbit has yet been obtained. The aim of our study was to determine an adequate dose of LPS to inject in growing rabbits in order to elicit a measurable inflammatory response in terms of plasmatic TNF-α and rise in rectal temperature. Three trials were carried out in this study: 2 development trials, the first (n=18) testing 3 doses of LPS (2, 10, 50 μg/kg) on the plasmatic TNF-α concentration at 90 and 180 min post injection, and the second trial (n=36) testing 4 doses of LPS (50, 75, 100 and 150 μg/kg) on the TNF-α concentration 90 min post injection and the rectal temperature. The third trial was designed as an application of the method in a large number of animals (n=32) to study the effect of feed restriction and dietary increase in digestible fibre to starch ratio on the LPS inflammatory challenge response of growing rabbits. In development trials 1 and 2, animals had measurable TNF-α responses for doses higher than 10 μg/kg at 90 min post injection, with an increase in the number of responsive animals along with the dose. High variability was observed in TNF-α concentrations in responsive animals (coefficient of variation from 44 to 94%). Animals demonstrated an increase in rectal temperature for all doses injected in the range of 50-150 μg/kg from 90 min post injection with a peak at 180 min (ΔTr =1.9±0.7°C). Our observations led us to choose a dose of 100 μg/kg of LPS for our following studies, as the responses in terms of temperature and TNF-α were the most satisfactory. The application of our LPS injection protocol to our nutritional study enabled us to validate our protocol (ΔTr =1.1±0.7°C at 180 min and 15/32 TNF-α responsive animals) even though we were not able to demonstrate any effect of the feeding level or diet on the inflammatory response to an LPS injection.