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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #78960
Title: ORAL ASPIRIN AND IBUPROFEN INCREASE CYTOKINE-INDUCED SYNTHESIS OF IL-1BETA AND OF TUMOR NECROSIS FACTOR-ALPHA EX VIVO

Author
item ENDRES, S - UNIV MUNICH
item WHITAKER, R - NEMC
item GHORBANI, R - NEMC
item MEYDANI, SIMIN - HNRCA-TUFTS
item DINARELLO, C - NEMC

Submitted to: Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: We investigated the effect of aspirin and ibuprofen on certain parameters of the immune system including cytokines, which are cells that regulate the duration and intensity of immune response, in healthy volunteers. Seven volunteers took 325 mg of aspirin daily for 14 days. Three weeks after ending aspirin medication, cytokines produced in response to other types of cytokines were found to be elevated while cytokines produced by other mechanisms of the immune system were not influenced by aspirin ingestion. In addition, other parameters of the immune system did not show any effect of aspirin. After 7 weeks, all parameters of the subjects' immune systems returned to normal, pre-aspirin levels. Another 7 volunteers took 200 mg of ibuprofen daily for 12 days. Again, there was no general effect other than in response to other cytokines. All levels returned to their pre-ibuprofen levels 5 weeks after stopping medication. Although aspirin and ibuprofen blunt such symptoms as fever and pain, their effect is not mediated through the production of cytokines. We conclude that short-term use of either medication results in an increase in cytokine-induced cytokine synthesis that is not observed in the production of cytokines by other stimulants such as bacteria.

Technical Abstract: We investigated the effect of oral aspirin and ibuprofen on the ex vivo synthesis of interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, tumor necrosis factor-a (TNF-a), 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-1b and TNF-a synthesis induced by exogenous IL-1a was elevated threefold compared to the pre-aspirin value (P=0.01 and P=0.05, 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 PGE2 production returned to pre-aspirin levels. Another 7 volunteers took 200 mg of ibuprofen daily for 12 days. Again, there was no effect on LPS- or Staphylococcus epidermis-induced cytokine synthesis. However, IL-1a-induced synthesis of IL-1b was elevated to a mean individual increase of 538% (P<0.001) and synthesis of TNF-a was elevated to 270% (P<0.001) at the end of the ibuprofen medication and 2 weeks after the discontinuation of ibuprofen. There were parallel increases in PGE2 and both returned to their pre-ibuprofen levels 5 weeks after stopping medication. Although inhibitors of cyclooxygenase 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.