BACKGROUND: Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MoAb) against IL-8 has been successfully used in some animal models of inflammation, no specific therapeutic agent against IL-8 has been tested for the treatment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endotoxic shock model. METHODS: Twenty New Zealand white rabbits were anesthetized 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 injection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 micrograms/kg). The normal group received NaCl (0.9%) rather 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 smaller decrease in mean arterial blood pressure (p < 0.05) and increased urinary 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 survival rate (p < 0.01). CONCLUSIONS: IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypotensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock.
BACKGROUND: Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MoAb) against IL-8 has been successfully used in some animal models of inflammation, no specific therapeutic agent against IL-8 has been tested for the treatment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endotoxic shock model. METHODS: Twenty New Zealand white rabbits were anesthetized 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 injection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 micrograms/kg). The normal group received NaCl (0.9%) rather 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-8rabbits had a smaller decrease in mean arterial blood pressure (p < 0.05) and increased urinary volume (p < 0.05). Anti-IL-8rabbits had lower plasmatic levels of IL-1 beta, less free radical production (p < 0.05), and a higher survival rate (p < 0.01). CONCLUSIONS:IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypotensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock.
Authors: Christopher S Davis; Scott E Janus; Michael J Mosier; Stewart R Carter; Jeffrey T Gibbs; Luis Ramirez; Richard L Gamelli; Elizabeth J Kovacs Journal: Ann Surg Date: 2013-06 Impact factor: 12.969
Authors: S Sakai; H Kawamata; N Mantani; T Kogure; Y Shimada; K Terasawa; T Sakai; N Imanishi; H Ochiai Journal: J Virol Date: 2000-03 Impact factor: 5.103
Authors: Peter A Szabo; Ram V Anantha; Christopher R Shaler; John K McCormick; S M Mansour Haeryfar Journal: Front Immunol Date: 2015-08-12 Impact factor: 7.561
Authors: Jose J Rosado-Franco; Marcos J Ramos-Benitez; Laura M Parodi; Derick Rosario; Nicole Compo; Luis D Giavedoni; Ana M Espino Journal: Animal Model Exp Med Date: 2019-10-08