OBJECTIVE: To test the hypothesis that antioxidants might affect local inflammation by impairing inflammatory cell influx. DESIGN: A laboratory study using a Swiss-Webster mouse model of local inflammation. SETTING: A university-affiliated hospital. METHODS: Intradermal injection of 30 micrograms of S. minnesota endotoxin (LPS) to Swiss-Webster mice initiates a local inflammatory reaction characterized by an early rise in vascular permeability and a later infux of neutrophils. Animals were pretreated intraperitoneally with either pyrrolidine dithiocarbamate (PDTC, 2 mmol/kg), which inhibits free radical generation, or dimethylthiourea (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) determined by iodine-125 albumin injection before sacrifice; neutrophil accumulation quantified by tissue myeloperoxidase levels; tissue levels of the endothelial adhesion molecules intercellular adhesion molecule-1 protein (ICAM-1) and vascular cell adhesion molecule-1 protein (VCAM-1) assessed by immunohistochemistry 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 influx. Both ICAM-1 and VCAM-1 were upregulated in response to LPS; however, only the increase in VCAM-1 was attenuated by antioxidant pretreatment. CONCLUSION: These data suggest that antioxidants disrupt the propagation phase of an inflammatory response possibly by altering neutrophil migration.
OBJECTIVE: To test the hypothesis that antioxidants might affect local inflammation by impairing inflammatory cell influx. DESIGN: A laboratory study using a Swiss-Webster mouse model of local inflammation. SETTING: A university-affiliated hospital. METHODS: Intradermal injection of 30 micrograms of S. minnesota endotoxin (LPS) to Swiss-Webster mice initiates a local inflammatory reaction characterized by an early rise in vascular permeability and a later infux of neutrophils. Animals were pretreated intraperitoneally with either pyrrolidine dithiocarbamate (PDTC, 2 mmol/kg), which inhibits free radical generation, or dimethylthiourea (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) determined by iodine-125 albumin injection before sacrifice; neutrophil accumulation quantified by tissue myeloperoxidase levels; tissue levels of the endothelial adhesion molecules intercellular adhesion molecule-1 protein (ICAM-1) and vascular cell adhesion molecule-1 protein (VCAM-1) assessed by immunohistochemistry 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 influx. Both ICAM-1 and VCAM-1 were upregulated in response to LPS; however, only the increase in VCAM-1 was attenuated by antioxidant pretreatment. CONCLUSION: These data suggest that antioxidants disrupt the propagation phase of an inflammatory response possibly by altering neutrophil migration.
Authors: Judith C Kim; Diana Whitaker-Menezes; Masatoshi Deguchi; Brigette S Adair; Robert Korngold; George F Murphy Journal: Am J Pathol Date: 2002-09 Impact factor: 4.307