bw-540c and Inflammation

An equine model of acute non-immune inflammation has been developed to facilitate studies of the inflammatory process and the actions of novel anti-inflammatory drugs. Five polyester sponge strips soaked in sterile 2% carrageenin solution were placed in subcutaneous pouches prepared under local anaesthesia in the necks of conscious ponies. Serial removal of the strips and harvesting of the exudate enabled studies to be made of the cellular, biochemical and mediator aspects of the localised, acute inflammation, and the heat generated by the lesion was monitored by infra-red thermometry. Maximal concentrations of the eicosanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotriene B4 occurred at 9 h, whereas leukocyte numbers, lactate dehydrogenase (LDH) and total protein concentrations were greatest at 24 h. Lesional skin temperature was increased by approximately 4 degrees C throughout the 24 h period. The novel anti-inflammatory agent BW540C, administered orally at a dose-rate of 20 mg/kg, did not affect leukocyte infiltration or the concentrations of protein, LDH and eicosanoids in exudate but serum thromboxane B2 levels were reduced. Skin temperature rises were greater in drug-treated animals. It is concluded that higher doses of BW540C will be required for a clinically useful anti-inflammatory action in horses.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Disease Models, Animal; Exudates and Transudates; Female; Horse Diseases; Horses; Inflammation; L-Lactate Dehydrogenase; Leukocyte Count; Leukotriene B4; Proteins; Pyrazoles; Skin Temperature; Thromboxane B2

In a two-part cross-over experiment in six ponies, an acute inflammatory reaction was generated by injecting carrageenin solution into subcutaneously-implanted tissue-cages lined with fibrovascular granulation tissue. In each part of the cross-over, half of the ponies received a novel phenylpyrazoline anti-inflammatory agent (BW540C) orally and half received a placebo treatment. BW540C inhibited platelet cyclo-oxygenase for 24 h but the reductions in exudate eicosanoid concentrations were less pronounced. A significant suppression in the rise of surface skin temperature in BW540C-treated ponies paralleled drug-induced inhibition of thromboxane B2 bicyclic prostaglandin (PG) E2 concentrations at the inflamed site. The drug had no significant effect on 6-keto-PGF1 alpha, migrating leucocytes, lactate dehydrogenase or total protein in exudates. Maximum plasma concentrations of both compounds occurred 2 to 4 h after dosing and maximum exudate levels of drug and metabolite occurred at 12 h. Both compounds penetrated approximately three times less readily into exudate than into plasma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Exudates and Transudates; Female; Horse Diseases; Horses; Inflammation; L-Lactate Dehydrogenase; Leukocyte Count; Male; Pyrazoles; Thromboxane B2