Application of in vitro methods using peripheral whole blood to selecting highly susceptible individuals among common squirrel monkeys (Saimiri sciureus) to bacterial lipopolysaccharides

The present study was designed to elucidate whether the individual suscepti bility of common squirrel monkeys (Saimiri sciureus) to bacterial lipopolys accharides (LPS) can be predicted by in vitro testing batteries performed i n advance. Of the in vitro tests, the blastogenic response (n = 11) to LPS was determined by a micro-blood culture technique, and the production (n = 6) of cytokines such as tumour necrosis factor (TNF-alpha), interleukin-1 ( IL-1 beta) and interleukin-6 (IL-6) released into the culture medium was me asured with an enzyme-linked immunosolvent assay (ELISA). In the blastogeni c assay, four out of 11 animals showed an increase in the uptake of [H-3]th ymidine in a concentration-dependent manner (LPS-positive reaction), while seven remaining animals did not show any response to LPS (LPS-negative reac tion). Among the cytokines employed, an elevation in TNF-alpha. production was noted in three out of six animals employed without affecting IL-1 beta and IL-6 productions. After the completion of in vitro examinations, LPS wa s administered subcutaneously at 0.3 mg/kg to these animals (n = 11) for 14 consecutive days. The six monkeys including either four animals showing a LPS-positive reaction or three animals having an increase in TNF-alpha prod uction exhibited moribund conditions from days 3 to 12, and five remaining monkeys including five animals showing a LPS-negative reaction or three ani mals having a decrease in TNF-alpha production survived. The extrapolation rate from the in vitro data to the in vivo results was over 80% (9/11) and 100% (6/6) in the blastogenic assay and TNF-alpha production, respectively. These results demonstrate that the in vitro methods can be available to se lection of LPS-sensitive squirrel monkeys in advance. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.