Figure 3. Inhibition of pre and post exposure to SEB -induced cytokine production by T5910047 in primary culture of human PBMC and survivability of mice treated with compound T5910047.

PBMCs (1 × 10⁶) from two normal donors were cultured for 20 h with SEB (200 ng/ml) with or without T5910047 (500 μM to 1 μM) treatment 30 min prior to SEB exposure (pre-exposure) or later (post exposure). The culture supernatants were collected and measured for cytokine by MSD assay as described in materials and methods. The data presented as cytokine production (pg/ml) and IC_50, calculated as the concentration of the inhibitor required for SEB-induced inhibition of cytokine production in PBMCs by 50% relative to the control (only with SEB treatment without inhibitor). (a) IFN-γ, IL-1β, IL-6 and TNF-α production and IC₅₀, pre-exposure to SEB. (b) IFN-γ, IL-1β, IL-6 and TNF-α production and IC₅₀, post-exposure to SEB. Data are the representation of two donors ; (c) In vivo efficacy of T5910047 - pre-treatment of T5910047 at 6 mg/mouse protected from lethal SEB challenge (P-Values ≤ 0.0131from log-rank test comparing the treated group and untreated group SEB(1.0 μg)+LPS.