Goscinski Gunilla, Lipcsey Miklos, Eriksson Mats, Larsson Anders, Tano Eva, Sjölin Jan
Section of Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Crit Care. 2004 Feb;8(1):R35-41. doi: 10.1186/cc2415. Epub 2003 Dec 23.
Antibiotics used for treatment of severe bacterial infections have been shown to exert effects on the inflammatory response in addition to their antibacterial effects. The aim of the present study was to investigate whether the biological effects of endotoxin in a porcine model could be neutralized by tobramycin, and whether tobramycin or ceftazidime was able to modulate the inflammatory response.
Thirteen piglets were subjected to endotoxin infusion at an initial rate of 4 microgram/kg per hour, which was reduced to 1 microgram/kg per hour after 30 min. Before endotoxin infusion, the animals received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically relevant doses. Physiological parameters were measured and blood samples were taken hourly for 6 hours for analysis of tumour necrosis factor-alpha, IL-6 and endotoxin concentrations.
All of the animals exhibited physiological signs of severe sepsis without major differences between the groups. Plasma endotoxin concentration was stable after 1 hour. There were no differences in endotoxin concentration or initial tumour necrosis factor-alpha and IL-6 concentrations between the groups. At 6 hours the IL-6 concentration was significantly lower in the ceftazidime group than in the saline group (P < 0.05), and in both the ceftazidime and the tobramycin groups there were significantly greater reductions from peak values (P < 0.05).
There was no neutralization of the biological effects of endotoxin in this porcine model. However, our data indicate a possible anti-inflammatory effect exerted by both ceftazidime and tobramycin, which manifested as a significantly greater reduction in IL-6 in comparison with the untreated group.
用于治疗严重细菌感染的抗生素除了具有抗菌作用外，还显示出对炎症反应有影响。本研究的目的是调查妥布霉素是否能中和猪模型中内毒素的生物学效应，以及妥布霉素或头孢他啶是否能够调节炎症反应。
13只仔猪以每小时4微克/千克的初始速率输注内毒素，30分钟后速率降至每小时1微克/千克。在内毒素输注前，动物接受临床相关剂量的生理盐水（n = 4）、头孢他啶（n = 5）或妥布霉素（n = 4）。测量生理参数，并每小时采集血样，持续6小时，以分析肿瘤坏死因子-α、白细胞介素-6和内毒素浓度。
所有动物均表现出严重脓毒症的生理体征，各组之间无重大差异。1小时后血浆内毒素浓度稳定。各组在内毒素浓度或初始肿瘤坏死因子-α和白细胞介素-6浓度方面无差异。6小时时，头孢他啶组的白细胞介素-6浓度显著低于生理盐水组（P < 0.05），并且在头孢他啶组和妥布霉素组中，与峰值相比均有显著更大程度的降低（P < 0.05）。
在该猪模型中，内毒素的生物学效应未被中和。然而，我们的数据表明头孢他啶和妥布霉素均可能具有抗炎作用，表现为与未治疗组相比，白细胞介素-6有显著更大程度的降低。
