A novel xanthine derivative counteracting in vivo tumor necrosis factor alpha toxicity in mice

The xanthine derivative A 802715 (1-(5-hydroxy-5-methyl)hexyl-3-methyl-7- propyl-xanthine, Hoechst AG) caused dose-dependent protection against lipopolysaccharide (LPS)-induced lethal shock in mice. In animals which had received the compound, the LPS-induced increase of serum tumor necrosis factor (TNF alpha) levels was not significantly affected. Protection against LPS-induced lethality was observed not only when A 802715 was given 1 hr before or simultaneously with LPS but also when administered 1 hr after LPS challenge. Administration of 200 mg/kg of the compound 1 hr before challenge also fully protected against lethal shock induced by intravenous administration of recombinant murine TNF alpha. It is concluded that A 802715 counteracts TNF alpha toxicity and that the drug bears the potential of therapeutic intervention in septic shock.