Actions of betamethasone in models of acute non-immune inflammation

Abstract

In an equine model of acute non-immune inflammation, betamethasone reduced polymorphonuclear cell infiltration into inflammatory exudates only when high doses (1 mg·kg −1) were administered intravenously and then only at 24 h. A clinical dose rate of the drug (80 μg·kg −1), administered intravenously as a single dose or daily for 4 d, significantly increased leucocyte numbers in exudates at some sampling times. The cause of this unexpected finding is unknown but it could be species specific, since a similar effect could not be demonstrated in a rat model of acute inflammation. Findings in the horse probably cannot be ascribed to a stabilizing action of betamethasone on cell or lysosomal membranes, since exudate concentrations of acid phosphatase were also increased. Inhibition of synthesis of the eicosanoids PGE 2, TXB 2, 6-keto-PGF 1α and LTB 4, did not occur with a single low dose (80 μg·kg −1) of betamethasone in horses. Although reduced exudate concentrations of some of these eicosanoids at some time intervals did occur after the administration of high doses (1 mg·kg −1) or multiple doses (4 × 80 μg·kg −1) of betamethasone to horses, the effect was inconsistent. The heat generated at the site of the inflammatory lesion was suppressed by betamethasone (1 mg·kg −1) for 12 h. These data fail to support the hypothesis that the anti-inflammatory action of betamethasone is attributable to inhibition of phospholipase A 2 and a consequent suppression of eicosanoid synthesis.