Ex Vivo Whole-Blood LPS Stimulation
The concentrations of TNF, IL-6, and IL-1 in blood increase after stimulation with bacterial lipopolysaccharide (LPS).
This short-term assay is often used as a first-pass screen for drugs aimed at treatment of rheumatoid arthritis (RA), prior to testing in the collagen-induced arthritis (CIA) model. Suppression of these cytokines has good predictive value for drug efficacy in CIA.
The test compound is administered to Lewis rats, then blood is collected 1 to 24 hours later.
From part of the collected blood, plasma is isolated for PK evaluation, and the remaining blood is used to set up in vitro stimulation with LPS (or other stimuli), followed by measurement of cytokine production with either ELISA or cytokine bead assay (CBA).
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