Interaction of indomethacin with cytokine production in whole blood. Potential mechanism for a brain-protective effect.
Both Alzheimer's disease and vascular dementia are featured by inflammatory responses and it is known that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk and severity of these diseases. To study the effect of NSAIDs on PGE2 levels and pro- and anti-inflammatory cytokine levels in the whole blood assay, blood samples from 23 elderly persons aged 85 years were stimulated with thrombin or LPS as primary stimulus. Indomethacin was added in concentrations ranging from 0.4 to 16 microg/ml and acetylsalicylic acid was added to in concentrations ranging from 0.5 to 8.0 microg/ml. Indomethacin abrogated thrombin- and LPS-induced PGE2 production at all concentrations tested. In addition, indomethacin reduced the production of thrombin-induced IL-6 and IL-10 (p<0.05) at physiological concentrations. Indomethacin reduced the production of LPS-induced IL-6, IL-1 beta and IL-10 (p<0.05) at the highest indomethacin concentration tested. Similar results were obtained upon incubation with acetylsalicylic acid. It is concluded that indomethacin may reduce the thrombin-induced inflammatory reaction by decreasing IL-6 through inhibition of PGE2 synthesis. This IL-6 reduction may be relevant for the ability of indomethacin to reduce the risk of Alzheimer's disease. However, the decrease in IL-10 production due to indomethacin suggests a more inflammatory state.
Bour
A M
AM
Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, LUMC Building 1 C2-R, P.O. Box 9600, 2300 Leiden RC, The Netherlands.
Westendorp
R G
RG
Laterveer
J C
JC
Bollen
E L
EL
Remarque
E J
EJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D001921:Brain / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D015232:Dinoprostone / Q000097:blood; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D013917:Thrombin / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D013917:Thrombin; D015232:Dinoprostone; D007213:Indomethacin