title: Application of in vitro methods using peripheral whole blood to selecting highly susceptible individuals among common squirrel monkeys (Saimiri sciureus) to bacterial lipopolysaccharides.
abstract: The present study was designed to elucidate whether the individual susceptibility of common squirrel monkeys (Saimiri sciureus) to bacterial lipopolysaccharides (LPS) can be predicted by in vitro testing batteries performed in 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-1beta) and interleukin-6 (IL-6) released into the culture medium was measured with an enzyme-linked immunosolvent assay (ELISA). In the blastogenic assay, four out of 11 animals showed an increase in the uptake of [3H]thymidine in a concentration-dependent manner (LPS-positive reaction), while seven remaining animals did not show any response to LPS (LPS-negative reaction). Among the cytokines employed, an elevation in TNF-alpha production was noted in three out of six animals employed without affecting IL-1beta and IL-6 productions. After the completion of in vitro examinations, LPS was 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 production exhibited moribund conditions from days 3 to 12, and five remaining monkeys including five animals showing a LPS-negative reaction or three animals 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 selection of LPS-sensitive squirrel monkeys in advance.
authors.affiliation: Tokyo Research and Development Center, Daiichi Pharmaceutical Co., Ltd, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Furuhama
mesh_terms: D000818:Animals; D001769:Blood / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D008213:Lymphocyte Activation; D011237:Predictive Value of Tests; D012453:Saimiri; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha