[Inhibitory effect of mouse antiendotoxin monoclonal antibody (E5) on hypotension induced by endotoxin and TNF-alpha]

Mouse anti-endotoxin monoclonal antibody (E5) is now under clinical trial (Phase II) in Japan by assessing clinical findings and plasma endotoxin levels. We attempted to evaluate an inhibitory effect of E5 on hypotension induced by endotoxin and TNF-alpha. Systolic blood pressure was measured with a programmable sphygmomanometer using the tail-cuff method. The mixture of endotoxin (E. coli O111:B4, Sigma, 2 micrograms/mouse) and recombinant mouse TNF-alpha (Genzyme, 8000 units) were injected into mice (ddY, 6-8-weeks-olds), and the change of blood pressure was observed for 3 hrs. The mixture significantly decreased the blood pressure to about 70% of the control. E5 (20 micrograms/mouse), which was injected 10 min before, significantly abrogated the effect of endotoxin and TNF-alpha. The hypotension induced by the mixture was definitely inhibited by the injection of E5 (50, 100 micrograms/mouse), injected 10 min later, or the injection of E5 (100 micrograms/mouse) 30 min later. We previously found that E5 prevents the lethality induced by a concomitant injection of endotoxin, TNF-alpha and IL-2. These results suggest that E5 effective for inhibition of endotoxin activity in vivo.