Nimesulide, indomethacin, BW 755 C, phenidon, mepacrin and nedocromil inhibit the activation of human and rat leucocytes.
This study confirms the strong inhibition of therapeutic concentrations of the antiinflammatory agent nimesulide (NI) on the chemiluminescence (CL) of human leucocytes (HL) after stimulation with opsonized zymosan (C3Z), and extends the findings to peritoneal (RPL) and bronchoalveolar leucocytes (RBAL) collected from actively immunized rats 24 h after i.v. injection of Sephadex. Additionally we demonstrate that NI is a strong inhibitor of proteinase release (PR) from HL. The reference drugs tested for comparison were indomethacin (I), BW 755 C (BW), phenidon (PH), mepacrin (M) and nedrocromil (NE). The rank order of potency for suppression of PR and CL was nearly independent of the cell type and stimulus: PH greater than or equal to BW greater than M greater than NI = 4-OH-NI much greater than I greater than NE. NI was the superior inhibitor of HL activation compared with I as measured either by PR or CL (factor 7), and also of CL of RPL and RBAL (factor 2-3). NI inhibited the PR from HL and CL of RPL or RBAL almost equipotently (IC30: 10-20 micrograms/ml), whereas PH, BW, M and I were 6-10 times more effective as CL inhibitors compared with their PR inhibition. In contrast NE showed a preferential inhibition of PR. This unique inhibition profile on leucocyte activation in vitro may be related to the differences of NI and I which are also existing in their antiinflammatory activities in vivo.
Wilhelms
O H
OH
Department of Mediator Pharmacology, Boehringer Mannheim GmbH, F.R. Germany.
Linssen
M J
MJ
Lipponer
L
L
Seilnacht
W
W
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors; D008163:Luminescent Measurements; D017835:Nedocromil; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D015363:Quinolones; D013449:Sulfonamides; D017835:Nedocromil; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D010741:Phospholipases A; D011796:Quinacrine; C015429:phenidone; C012655:nimesulide; D007213:Indomethacin