Tocainide suppression of immune-complex-mediated dermal inflammation: Comparison with prostaglandin E1

Abstract

Local anesthetic agents have been shown to alter a variety of polymorphonuclear leukocyte (PMN) functions and may be useful as anti-inflammatory agents. We compared the anti-inflammatory effects of therapeutic doses of the recently released local anesthetic-antiarrythmic drug tocainide to pharmacologic doses of prostaglandin E1 (PGE1) on immune-complex-mediated dermal inflammation in female Sprague-Dawley rats. Intense dermal inflammation was produced using a classic reverse passive Arthus reaction, and the inhibition of PMN accumulation in the subdermis was quantitated in biopsy samples taken 2.5 hr after the reaction was initiated and the drug was given. Using a light microscope with a counting grid, biopsy sections were randomly sampled in a blinded fashion and an inflammation index equal to the ratio of PMNs to fibroblasts was determined for each animal. The mean inflammation index in 10 animals given 25 mg of tocainide (mean serum level = 14.6 μg/ml) was 9.3 ± 1.2 (±SEM), which was significantly less than the index of 17.7 ± 2.5 in 10 control animals ( P < 0.025). Similarly, the five animals that received either 500 or 250 μg of PGE1 had a significantly reduced index, with the effect of 250 μg PGE1 comparable to the effect of the tocainide. These findings suggest that therapeutic levels of tocainide reduce the accumulation of PMNs in immune-complex-mediated dermal inflammation; thus, local anesthetic agents may be useful in the treatment of certain inflammatory disorders.