Endres S, Whitaker R E, Ghorbani R, Meydani S N, Dinarello C A
New England Medical Center Hospitals and Tufts University School of Medicine, Boston, MA, USA.
Immunology. 1996 Feb;87(2):264-70. doi: 10.1046/j.1365-2567.1996.472535.x.
We investigated the effect of oral aspirin and ibuprofen on the ex vivo synthesis of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by stimulated peripheral blood mononuclear cells (PBMC) from healthy volunteers. Seven volunteers took 325 mg of aspirin daily for 14 days. Three weeks after ending aspirin medication, ex vivo IL-1 beta and TNF synthesis induced by exogenous IL-1 alpha was elevated threefold compared to the pre-aspirin value (P = 0.01 and P = 0.005, respectively). Using lipopolysaccharide (LPS) as a stimulus, no influence of oral aspirin was observed. The increase in cytokine synthesis did not parallel decreased synthesis of prostaglandin E2 (PGE2). Seven weeks after discontinuation of aspirin, cytokine and PGE-2 production returned to pre-aspirin levels. Another seven volunteers took 200 mg of ibuprofen daily for 12 days. Again, there was no effect on LPS- or Staphylococcus epidermidis-induced cytokine synthesis. However, IL-1 alpha-induced synthesis of IL-1 beta was elevated to a mean individual increase of 538% (P < 0.001) and synthesis of TNF was elevated to 270% (P < 0.001) at the end of ibuprofen medication and 2 weeks after discontinuation of ibuprofen. There were parallel increases in PGE2 and both returned to their pre-ibuprofen levels 5 weeks after stopping. Although inhibitors of cyclo-oxygenase blunt PGE2-mediated symptoms such as fever and pain, we conclude that short term use of either aspirin or ibuprofen results in a 'rebound' increase in cytokine-induced cytokine synthesis that is not observed in LPS-induced cytokines.
我们研究了口服阿司匹林和布洛芬对健康志愿者外周血单个核细胞（PBMC）体外合成白细胞介素-1α（IL-1α）、IL-1β、IL-2、IL-6、肿瘤坏死因子-α（TNF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的影响。7名志愿者每天服用325毫克阿司匹林，持续14天。停止服用阿司匹林药物3周后，外源性IL-1α诱导的IL-1β和TNF体外合成较服用阿司匹林前的值升高了三倍（分别为P = 0.01和P = 0.005）。使用脂多糖（LPS）作为刺激物时，未观察到口服阿司匹林有影响。细胞因子合成的增加与前列腺素E2（PGE2）合成的减少不平行。停用阿司匹林7周后，细胞因子和PGE-2的产生恢复到服用阿司匹林前的水平。另外7名志愿者每天服用200毫克布洛芬，持续12天。同样，对LPS或表皮葡萄球菌诱导的细胞因子合成没有影响。然而，在布洛芬用药结束时以及停用布洛芬2周后，IL-1α诱导的IL-1β合成平均个体增加至538%（P < 0.001），TNF合成增加至270%（P < 0.001）。PGE2也有平行增加，停药5周后两者均恢复到服用布洛芬前的水平。尽管环氧化酶抑制剂可减轻PGE2介导的症状，如发热和疼痛，但我们得出结论，短期使用阿司匹林或布洛芬会导致细胞因子诱导的细胞因子合成“反弹”增加，而在LPS诱导的细胞因子中未观察到这种情况。
