Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows

In this study, ex vivo assays were carried out in dairy cows to evaluate the anti- inflammatory effects of two nonsteroidal anti-inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti-inflammatory effects of both drugs were determined by measuring the production of coagulation-induced thromboxane B2 (TXB2), lipopolysaccharides (LPS) (10 lg ⁄ mL)-induced prostaglandin E2 (PGE2), and calcium ionophore (60 lM)-induced leukotrien B4 (LTB4). Cytokine production was assessed by measuring tumor necrosis factor-a (TNF-a), interferon-c (IFN-c) and interleu- kin-8 (CXCL8) concentrations after incubation in the presence of 10 lg ⁄ mL LPS. The IC50 of FM and KETO was determined in vitro by determining the concentration of TXB2 and PGE2 in the presence of scalar drug concentrations (10)9–10)3 M). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX-1. FM and KETO showed similar anti-inflamma- tory effects in the cow.