title: Oral aspirin and ibuprofen increase cytokine-induced synthesis of IL-1 beta and of tumour necrosis factor-alpha ex vivo.
abstract: 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.
authors.affiliation: New England Medical Center Hospitals and Tufts University School of Medicine, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Endres
authors.forename: R E
authors.initials: RE
authors.lastname: Whitaker
authors.forename: R
authors.initials: R
authors.lastname: Ghorbani
authors.forename: S N
authors.initials: SN
authors.lastname: Meydani
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000284:Administration, Oral; D000942:Antigens, Bacterial / Q000276:immunology; D001241:Aspirin / Q000008:administration & dosage / Q000276:immunology*; D018929:Cell Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007378:Interleukins / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D010835:Phytohemagglutinins / Q000276:immunology; D013212:Staphylococcus epidermidis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000942:Antigens, Bacterial; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007378:Interleukins; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin; D007052:Ibuprofen