Comparison of the effects of glucocorticoid and indomethacin treatment on the acute inflammatory reaction in rabbits

We have recently shown that indomethacin and ASA diminish the elevated blood flow, protein exudation, and leukocyte infiltration during acute inflammation induced by killed Escherichia coli, the reversed Arthus reaction, or zymosan-activated plasma (ZAP; C5a_des-arg) in rabbit skin. All of these effects were likely due to the inhibition by these drugs of prostaglandin (PG) synthesis in the lesions. Because glucocorticoids are also reported to inhibit PG production and, in large doses, to suppress inflammation accompanying various clinical conditions, we investigated the effects of hydrocortisone (HC), and methylprednisolone (MP), administered in large doses (100 mg/m²/d of MP or 2.5 g/m²/d of HC) on the above three forms of acute inflammation in rabbits. The effect of indomethacin treatment was studied in parallel for comparison. Blood flow, protein exudation, and leukocyte infiltration were quantitated simultaneously with ⁸⁶Rb Cl, ¹²⁵I-labelled rabbit albumin and ⁵¹Cr labelled blood leukocytes. Systemic indomethacin therapy decreased the blood flow and permeability, while local indomethacin (2.5 μg) significantly inhibited leukocyte infiltration into the lesions. In contrast, HC and MP caused only a mild decrease in blood flow, without altering protein exudation or leukocyte influx. However, HC and MP did inhibit protein exudation induced by bradykinin or histamine injection. These results indicate that, at least in rabbits, HC and MP, in contrast to indomethacin, have very weak anti-inflammatory actions on three complement- and neutrophil-mediated inflammatory responses, i.e., E. coli, ZAP (C5a_des-arg) and reversed Arthus reactions.