Etanercept and Infliximab, Two Tumor Necrosis Factor-α (TNF-α) Inhibitors With Different Action Profiles: An In vitro and In Vivo Study in the Context of Reviewed Therapeutic Applications

Abstract

Tumor necrosis factor-α (TNF-α) is a cytotoxic cytokine in vitro. It mediates septic shock, apoptosis, and inflammation in vivo. The in vitro work was used for testing the effect of Etanercept (ETA) and Infliximab (INF) against cell cytotoxicity caused by TNF-α. At the same time, the in vivo work was used to test the effect of the two tested agents on TNF-α serum levels in rats induced by lipopolysaccharides (LPS). Upon in vitro testing of the protective effect of both agents on the WI38 cells, it was found that ETA was superior to INF for antagonizing the effect of TNF-α whether the tested agent and TNF-α were simultaneously added to the cell line or the antibody addition proceeded TNF-α addition. In vivo testing of the effect of both agents showed that they significantly antagonized the effect of TNF-α with superior effect in case of ETA whether each tested agent was administered at four doses separated by one-week interval before LPS injection or it was administered once 24 hours after LPS administration. This study gave evidence for a differential antagonizing effect of ETA and INF against TNF-α with superior action in the case of ETA when they were assessed both in vitro and in vivo.