ORAL ASPIRIN AND IBUPROFEN INCREASE CYTOKINE-INDUCED SYNTHESIS OF IL-1-BETA AND OF TUMOR-NECROSIS-FACTOR-ALPHA EX-VIVO

We investigated the effect of oral aspirin and ibuprofen on the ex viv o 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 mononuclea r cells (PBMC) from healthy volunteers. Seven volunteers took 325 mg o f aspirin daily for 14 days. Three weeks after ending aspirin medicati on, ex vivo IL-1 beta and TNF synthesis induced by exogenous IL-1 alph a was elevated threefold compared to the pre-aspirin value (P = 0.01 a nd P = 0.005, respectively). Using lipopolysaccharide (LPS) as a stimu lus, no influence of oral aspirin was observed. The increase in cytoki ne synthesis did not parallel decreased synthesis of prostaglandin E(2 ) (PGE(2)). Seven weeks after discontinuation of aspirin, cytokine and PGE-(2) production returned to pre-aspirin levels. Another seven volu nteers took 200 mg of ibuprofen daily for 12 days. Again, there was no effect on LPS- or Staphylococcus epidermidis-induced cytokine synthes is. 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 w as elevated to 270% (P < 0.001) at the end of ibuprofen medication and 2 weeks after discontinuation of ibuprofen. There were parallel incre ases in PGE(2) and both returned to their pre-ibuprofen levels 5 weeks after slopping. Although inhibitors of cyclo-oxygenase blunt PGE(2)-m ediated symptoms such as fever and pain, we conclude that short term u se of either aspirin or ibuprofen results in a 'rebound' increase in c ytokine-induced cytokine synthesis that is not observed in LPS-induced cytokines.