SR-31747

Animal experiment:

IL-1, IL-6 and TNF-a are induced by i.p. injection of LPS into BALBIc mice. SR 31747 or reference substances are administered i.p. at the indicated doses together with LPS (0.5 mg/kg). Control animals are treated with LPS and vehicle. Blood samples are collected from the retro-orbital sinus 1 hr or 4 hr after LPS injection for the determination of TNF-α, IL-1 and IL-6. Plasma is prepared and stored frozen until experiments. The IL-1 plasma level is determined by a competitive radioreceptor assay with the use of the murine NOBEL4 cell line and [125I]-IL-1. The IL-6 assay is conducted with the B9 murine IL-6-dependent cell line. The TNF-a plasma level is evaluated by the cytolytic assay with the dactinomycin-treated LM6 cell line, derived from the murine fibroblastic L929 cell line. Each determination is performed on a pool of three different plasma samples. None of the molecules administered affect these assays even at the highest dose (10-5 M), which thereby rules out the possibility of any direct effect caused by the presence ofdrugs in treated-animal sera. In the various tests, one unit is defined as the amount of cytokines able to induce 50% of the maximal effect.

References:

[1]. Derocq JM, et al. In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by the sigma ligand SR 31747. J Pharmacol Exp Ther. 1995 Jan;272(1):224-30.
[2]. Silve S, et al. The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Jun;16(6):2719-27.