Development of an in Vivo Lipopolysaccharide Inflammation Model to Study the Pharmacodynamics of COX-2 Inhibitors Celecoxib, Mavacoxib, and Meloxicam in Cockatiels (Nymphicus hollandicus).

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used frequently in avian medicine for their antipyretic, analgesic, and anti-inflammatory properties during surgery and for diseases that cause tissue damage and inflammation. NSAIDs inhibit cyclooxygenase (COX) enzymes, which are responsible for the induction of pyresis, pain, and inflammation. In our study, a lipopolysaccharide-induced (LPS) pyresis model was optimized using cockatiels (Nymphicus hollandicus) as subject birds (four males/three females) and validated in two females and one male, characterized by an intravenous bolus injection of LPS (7.5 mg/kg) administered at T0 and T24 (24 hours following the first LPS injection). To demonstrate the feasibility of the model to assess pharmacodynamic (PD) parameters of different NSAIDs, mavacoxib 4 mg/kg (four males/four females), celecoxib 10 mg/kg (four males/four females) and meloxicam 1 mg/kg (four males/four females) were evaluated in the model at dosages used frequently in practice. The PD parameters (body temperature, mentation, posture, preference of location in the cage, and prostaglandin E2 [PGE2] plasma concentrations) were determined for 10 hours following the second LPS injection. At the doses evaluated, mavacoxib and celecoxib significantly reduced LPS-induced hypothermia, but had no clear effects on other clinical signs of illness. In contrast, no effect on hypothermia or clinical appearance was observed in the LPS-challenged cockatiels treated with meloxicam. All three NSAIDs were able to inhibit the increase in LPS-induced PGE2 plasma concentrations, yet the effect was most pronounced in the birds treated with meloxicam. Consequently, the presented model opens perspectives for future dose-effect PD studies to optimize analgesic protocols in cockatiels.