Mansilla-Roselló A, Ferrón-Orihuela J A, Ruiz-Cabello F, Garrote-Lara D, Fernández-Mondéjar E, Delgado-Carrasco M L
Experimental Surgery Unit, Virgen de las Nieves Foundation, Granada, Spain.
J Surg Res. 1997 Feb 1;67(2):199-204. doi: 10.1006/jsre.1996.4982.
Interleukin-1 (IL-1) and ibuprofen modulate the host response in different models after endotoxic challenge. A comparative study was made between the two drugs, as they were jointly administered, to explore a potentiation of their therapeutic effects. Endotoxic challenge was provoked in CBA/H mice with lipopolysaccharide (LPS) from Escherichia coli (125 mg/kg), with administration of recombinant murine IL-1 beta (80 ng/mouse) 24 hr pre-LPS. Two doses of ibuprofen (1 mg/kg) were administered 1 hr before and 30 min after the septic challenge. Serum levels of IL-1 alpha, tumor necrosis factor-alpha (TNF alpha), and interleukin-6 (IL-6) were determined 1,2, and 4 hr, post-LPS, and prostaglandin E2 (PGE2) urine levels 4,8, and 12 hr post-LPS, and a comparative mortality study was performed. IL-1 beta treatment provoked a reduction of IL-1 alpha, TNF alpha, and IL-6 without affecting PGE2, while ibuprofen provoked a later increase of IL-1 alpha, TNF alpha, and IL-6, with a decrease of PGE2. Both drugs caused a notable enhancement of survival, with no difference between them, but their combined administration caused no improvement. We conclude that both drugs exert a similar therapeutic effect in endotoxic shock by different mechanisms.
白细胞介素-1（IL-1）和布洛芬在内毒素攻击后的不同模型中调节宿主反应。对这两种药物联合给药时进行了一项比较研究，以探索其治疗效果的增强作用。用来自大肠杆菌的脂多糖（LPS，125mg/kg）对CBA/H小鼠进行内毒素攻击，在给予LPS前24小时给予重组鼠IL-1β（80ng/小鼠）。在脓毒症攻击前1小时和攻击后30分钟给予两剂布洛芬（1mg/kg）。在给予LPS后1、2和4小时测定血清IL-1α、肿瘤坏死因子-α（TNFα）和白细胞介素-6（IL-6）水平，在给予LPS后4、8和12小时测定前列腺素E2（PGE2）尿水平，并进行了一项比较死亡率研究。IL-1β治疗导致IL-1α、TNFα和IL-6减少，而不影响PGE2，而布洛芬导致IL-1α、TNFα和IL-6随后增加，同时PGE2减少。两种药物均显著提高了生存率，二者之间无差异，但联合给药并未带来改善。我们得出结论，两种药物通过不同机制在内毒素休克中发挥相似的治疗作用。
