Antioxidant modulation of skin inflammation: preventing inflammatory progression by inhibiting neutrophil influx.
OBJECTIVE
To test the hypothesis that antioxidants might affect local inflammation by impairing inflammatory cell influx.


METHODS
A laboratory study using a Swiss-Webster mouse model of local inflammation.


METHODS
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.


METHODS
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.


CONCLUSIONS
These data suggest that antioxidants disrupt the propagation phase of an inflammatory response possibly by altering neutrophil migration.
McGilvray
I D
ID
Department of Surgery, University of Toronto, Ont.
Rotstein
O D
OD
D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002199:Capillary Permeability; D003872:Dermatitis / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D000975:Antioxidants; D019010:Vascular Cell Adhesion Molecule-1