Inhibition of prostaglandin biosynthesis in human endotoxin-stimulated peripheral blood monocytes: effects of caffeine.
There is an ongoing debate about possible advantages of the coadministration of caffeine with cyclooxygenase (COX) inhibitors in the treatment of pain. There are results suggesting interference by caffeine with COX expression and activity in rat immune cells. In the present study, we have used, therefore, human endotoxin-stimulated monocytes to investigate a possible influence of caffeine on indometacin-induced inhibition of prostaglandin E(2) (PGE(2)) formation. Endotoxin caused a concentration- and time-dependent increase in immunoreactive PGE(2) that was dependent on CD14-mediated mechanisms. In order to investigate pharmacological inhibition of the COX activity, a submaximal concentration of 1 ng/ml endotoxin (4 h exposure time) was used. Indometacin caused a concentration-dependent inhibition of PGE(2) with an apparent IC(50) of 8.9 +/- 1.4 x 10(-9) mol/l and an I(max) of 1 x 10(-7) mol/l. Caffeine (5 x 10(-6) to 1.5 x 10(-4) mol/l) on its own produced no statistically significant effect on endotoxin-induced PGE(2) formation. In the presence of caffeine (5 x 10(-6) to 1.5 x 10(-4) mol/l), inhibition of PGE(2) biosynthesis by indometacin (1 x 10(-8) mol/l) was not significantly altered. These results show that, in human monocytes, caffeine, up to concentrations severalfold higher than those reached in patients, has no significant effect on endotoxin-induced PGE(2) formation nor on its inhibition by indometacin.
Ulcar
R
R
Institute of Experimental and Clinical Pharmacology, University of Graz, Austria.
Schuligoi
R
R
Heinemann
A
A
Santner
B
B
Amann
R
R
D002110:Caffeine / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases; D018709:Statistics, Nonparametric
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D002110:Caffeine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin