Precision cut lung slices (PCLS) as a tool to predict effective LPS concentrations for in vivo use in common marmoset monkeys

In this study a LPS-induced model for pulmonary inflammation was established in the South American non-endangered non-human primate Callithrix jacchus (common marmoset monkey), to provide an animal model resembling to the human situation. Two LPS formulations were tested on marmoset lung tissue with the ex vivo technique PCLS. Lung slices (~250 µm) were cultured submerse and exposed to LPS from two E. coli strains (O55:B5; O111:B4) in different concentrations (4-220 ng/ml). The pro-inflammatory cytokine TNF-alpha, was quantified by ELISA and histological HE-staining was performed. In an in vivo approach, two concentrations of LPS were applied segmentally into the right lung lobe with a MicroSprayer® as an aerosol, while the left lobe of the same animal served as control. Blood was analyzed before and after LPS provocation, cytokines in serum and tissue were quantified by ELISA. Inflammation was quantified in histological sections. In PCLS, both LPS triggered pro-inflammatory effects in a concentration dependent manner. However, E. coli O111:B4 induced the best dose-response-relationship. Therefore, this LPS-formulation was tested in vivo (4 and 220 ng/ml) and the results resembled those from the PCLS study. LPS concentration of 220 ng/ml induced a local inflammatory response in lung tissue, which was assessed by histology. Signs of systemic inflammation were absent. A concentration of 4 ng/ml LPS did not induce detectable effects in the lung. 220 ng/ml LPS tested ex vivo had a comparable effect in the in vivo system indicating that the PCLS system is a suitable tool to appraise LPS concentrations for save in vivo use.