TY - JOUR
T1 - Dose-dependent immunomodulatory effects of acetylsalicylic acid and indomethacin in human whole blood: Potential role of cyclooxygenase-2 inhibition
AU - Härtel, C.
AU - Von Puttkamer, J.
AU - Gallner, F.
AU - Strunk, T.
AU - Schultz, Christian
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/10
Y1 - 2004/10
N2 - The aim of the study was to characterize the in vitro effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of pro-inflammatory cytokines in a human whole blood assay. Whole blood samples were pre-incubated with acetylsalicylic acid, indomethacin, selective cyclooxygenase (COX)-1 inhibitor (SC-560), COX-2 inhibitor (NS-398) or prostaglandin E2 (PGE2) before stimulation with lipopolysaccharide (LPS). Pro-inflammatory and anti-inflammatory cytokines were determined directly at the cell level with the help of flow cytometry and/or in the plasma supernatant with the help of ELISA. High doses of acetylsalicylic acid were needed to inhibit pro-inflammatory cytokine production. In contrast, low-to-moderate doses induced a modestly enhanced production of pro-inflammatory cytokines. Moreover, indomethacin was demonstrated to increase the expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in a dose-dependent fashion. Upon addition of PGE2, however, LPS-induced IL-6 and TNF-α production was suppressed regardless of indomethacin presence. Interestingly, selective COX-2 inhibition (NS-398), but not selective COX-1 inhibition (SC-560), exerted a stimulatory effect on the expression of pro-inflammatory cytokines. These data emphasize that the immunomodulating effects of NSAIDs in whole blood are dose-dependent. Furthermore, the induction of pro-inflammatory cytokine expression by NSAIDs is potentially mediated by COX-2 inhibition. Although NSAIDs are successfully used in clinical practice for their net anti-inflammatory properties, our observations may contribute to the understanding of side effects induced by NSAIDs and selective COX-2 inhibitors.
AB - The aim of the study was to characterize the in vitro effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of pro-inflammatory cytokines in a human whole blood assay. Whole blood samples were pre-incubated with acetylsalicylic acid, indomethacin, selective cyclooxygenase (COX)-1 inhibitor (SC-560), COX-2 inhibitor (NS-398) or prostaglandin E2 (PGE2) before stimulation with lipopolysaccharide (LPS). Pro-inflammatory and anti-inflammatory cytokines were determined directly at the cell level with the help of flow cytometry and/or in the plasma supernatant with the help of ELISA. High doses of acetylsalicylic acid were needed to inhibit pro-inflammatory cytokine production. In contrast, low-to-moderate doses induced a modestly enhanced production of pro-inflammatory cytokines. Moreover, indomethacin was demonstrated to increase the expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in a dose-dependent fashion. Upon addition of PGE2, however, LPS-induced IL-6 and TNF-α production was suppressed regardless of indomethacin presence. Interestingly, selective COX-2 inhibition (NS-398), but not selective COX-1 inhibition (SC-560), exerted a stimulatory effect on the expression of pro-inflammatory cytokines. These data emphasize that the immunomodulating effects of NSAIDs in whole blood are dose-dependent. Furthermore, the induction of pro-inflammatory cytokine expression by NSAIDs is potentially mediated by COX-2 inhibition. Although NSAIDs are successfully used in clinical practice for their net anti-inflammatory properties, our observations may contribute to the understanding of side effects induced by NSAIDs and selective COX-2 inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=4944250059&partnerID=8YFLogxK
U2 - 10.1111/j.0300-9475.2004.01481.x
DO - 10.1111/j.0300-9475.2004.01481.x
M3 - Journal articles
C2 - 15379866
AN - SCOPUS:4944250059
SN - 0300-9475
VL - 60
SP - 412
EP - 420
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
IS - 4
ER -