ANTI-INTERLEUKIN-8 MONOCLONAL-ANTIBODY REDUCES FREE-RADICAL PRODUCTION AND IMPROVES HEMODYNAMICS AND SURVIVAL RATE IN ENDOTOXIC-SHOCK IN RABBITS

Background. Although high levels of interleukin-8 (IL-8) have been fou nd in patients with sepsis and a monoclonal antibody (MaAb) against IL -8 has been successfully used in some animal models of inflammation, n o specific therapeutic agent against IL-8 has been tested for the trea tment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endo toxic shock model. Methods. Twenty New Zealand white rabbits were anes thetized and divided into four groups: normal, anti-IL-8, control-Ab, and lipopolysaccharide (LPS). Anti-IL-8 and control-Ab groups received a MoAb immunoglobulin G, 3 mg/kg) 5 minutes before the LPS infection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 mu g/kg). The normal group received NaCl (0.9%) r ather than LPS. Results. The 7-day survival rates were 100% for normal group, 80% for anti-IL-8 group, 40% for control-Ab group, and 0% for LPS group. Compared with the LPS group, anti-IL-8 rabbits had a smalle r decrease in mean arterial blood pressure (p < 0.05) and increased ur inary volume (p < 0.05). Anti-IL-8 rabbits had lower plasmatic levels of IL-1 beta, less free radical production (p < 0.05), and a higher su rvival rate (p < 0.01). Conclusions. IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypot ensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock.