Stefan Endres1, Roy Whitaker2, R Ghorbani2, Simin Nikbin Meydani3, Charles A. Dinarello2
1New England Medical Center Hospitals and Tufts University School of Medicine, Boston, MA, USA.
2Department of Medicine, New England Medical Center Hospitals and Tufts University School of Medicine
3USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA USA
Tóm tắt
We investigated the effect of oral aspirin and ibuprofen on the ex vivo synthesis of interleukin‐1α (IL‐1α), IL‐1β, IL‐2, IL‐6, tumour necrosis factor‐α (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‐1β and TNF synthesis induced by exogenous IL‐1α 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‐1α‐induced synthesis of IL‐1β 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.
