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Antioxidant modulation of skin inflammation: preventing inflammatory progression by inhibiting neutrophil influx
1Department of Surgery, University of Toronto, Ont.
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.
Insights
Antioxidants, such as pyrrolidine dithiocarbamate (PDTC) and dimethylthiourea (DMTU), reduced neutrophil influx and vascular permeability during inflammation. These findings suggest antioxidants may impair inflammatory cell migration.
Area of Science:
- Immunology
- Pharmacology
- Biomedical Research
Background:
- Local inflammation involves increased vascular permeability and neutrophil influx.
- Free radicals play a role in inflammatory processes.
- Antioxidants are investigated for their potential to modulate inflammatory responses.
Purpose of the Study:
- To investigate the effect of antioxidants on inflammatory cell influx in a mouse model.
- To test if antioxidants can impair the inflammatory response by affecting neutrophil migration.
Main Methods:
- A laboratory study utilizing a Swiss-Webster mouse model of local inflammation induced by lipopolysaccharide (LPS).
- Mice were pretreated with pyrrolidine dithiocarbamate (PDTC) or dimethylthiourea (DMTU), known antioxidants.
- Vascular permeability, neutrophil accumulation (myeloperoxidase levels), and adhesion molecules (ICAM-1, VCAM-1) were assessed.
Main Results:
- Both PDTC and DMTU reduced late-phase vascular permeability and neutrophil influx.
- Antioxidant pretreatment attenuated the increase in vascular cell adhesion molecule-1 (VCAM-1) but not intercellular adhesion molecule-1 (ICAM-1).
- Early vascular permeability changes were not significantly affected by the antioxidants.
Conclusions:
- Antioxidants appear to disrupt the propagation phase of inflammation.
- The mechanism may involve altering neutrophil migration and adhesion molecule expression.
- These findings support a role for antioxidants in modulating local inflammatory responses.