Antioxidant modulation of skin inflammation: Preventing inflammatory progression by inhibiting neutrophil influx

OBJECTIVE: To test the hypothesis that antioxidants might affect local infl ammation by impairing inflammatory cell influx. DESIGN: A laboratory study using a Swiss-Webster mouse model of local infla mmation. SETTING: A university-affiliated hospital. METHODS: Intradermal injection of 30 mu g of S. minnesota a endotoxin (LPS) to Swiss-Webster mice initiates a local inflammatory reaction characterize d by an early rise in vascular permeability and a later influx of neutrophi ls. Animals were pretreated intraperitoneally with either pyrrolidine dithi ocarbamate (PDTC, 2 mmol/kg), which inhibits fi ee radical generation, or d imethylthiourea (DMTU, 450 mg/kg), a free radical scavenger. MAIN OUTCOME MEASURES: Histologic findings of tissue samples taken at sites of injection; local changes in tissue vascular permeability (PI) determine d by iodine-125 albumin injection before sacrifice; neutrophil accumulation quantified by tissue myeloperoxidase levels; tissue levels of the endothel ial adhesion molecules intercellular adhesion molecule-1 protein (ICAM-1) a nd vascular cell adhesion molecule-1 protein (VCAM-1) assessed by immunohis tochemistry and Western blot, respectively. RESULTS: Neither antioxidant had a significant effect on the early increase in PI, but both decreased the late rise in PI and reduced neutrophil influ x. Both ICAM-1 and VCAM-1 were upregulated in response to LPS; however, onl y the increase in VCAM-1 was attenuated by antioxidant pretreatment. CONCLUSION: These data suggest that antioxidants disrupt the propagation ph ase of an inflammatory response, possibly by altering neutrophil migration.