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 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.
Carvalho
G L
GL
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Wakabayashi
G
G
Shimazu
M
M
Karahashi
T
T
Yoshida
M
M
Yamamoto
S
S
Matsushima
K
K
Mukaida
N
N
Clark
B D
BD
Takabayashi
T
T
Brandt
C T
CT
Kitajima
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D004231:Diuresis; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006400:Hematocrit; D006439:Hemodynamics / Q000276:immunology / Q000502:physiology*; D007375:Interleukin-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D009504:Neutrophils / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000401:mortality* / Q000503:physiopathology* / Q000628:therapy; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005609:Free Radicals; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha