Anti-interleukin-8 monoclonal antibody reduces free radical production and improves hemodynamics and survival rate in endotoxic shock in rabbits

被引:34
作者
Carvalho, GL
Wakabayashi, G
Shimazu, M
Karahashi, T
Yoshida, M
Yamamoto, S
Matsushima, K
Mukaida, N
Clark, BD
Takabayashi, T
Brandt, CT
Kitajima, M
机构
[1] KEIO UNIV,SCH MED,DEPT SURG,LIVER TRANSPLANATAT DIV,SHINJUKU KU,TOKYO 160,JAPAN
[2] UNIV FED PERNAMBUCO,MASTERS COURSE SURG,RECIFE,PE,BRAZIL
[3] UNIV TOKYO,GRAD SCH MED,DEPT MOL PREVENT MED,TOKYO,JAPAN
[4] KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN
[5] TUFTS UNIV,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111
[6] TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111
[7] HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115
[8] MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114
关键词
D O I
10.1016/S0039-6060(97)90265-8
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MaAb) 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 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%) 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.
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页码:60 / 68
页数:9
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