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Ketotifen prevents skin fibrosis in the tight skin mouse
M Walker1, R Harley, E C LeRoy
1Department of Medicine, Medical University of South Carolina, Charleston.
Abstract:
Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma.
Insights
Mast cells degranulate more in tight-skin mice. Ketotifen, a mast cell inhibitor, reduced this degranulation and skin fibrosis, suggesting potential for treating human scleroderma.
Area of Science:
- Dermatology
- Immunology
- Pharmacology
Background:
- Mast cells play a role in inflammatory skin conditions.
- The tight-skin mouse model exhibits increased mast cell degranulation and skin fibrosis.
- Scleroderma is a fibrotic skin disease with unclear pathogenesis.
Purpose of the Study:
- To investigate the role of mast cell degranulation in the tight-skin mouse model.
- To evaluate the efficacy of ketotifen, a mast cell stabilizer, in mitigating skin fibrosis in this model.
Main Methods:
- Comparison of mast cell degranulation in tight-skin mice versus control litter mates.
- Oral administration of ketotifen at a human-equivalent dose to tight-skin mice.
- Assessment of mast cell degranulation and skin fibrosis following treatment.
Main Results:
- Mast cells in tight-skin mice demonstrated significantly enhanced degranulation compared to controls.
- Ketotifen treatment led to a reduction in mast cell degranulation.
- Ketotifen administration was associated with decreased skin fibrosis in the tight-skin mouse model.
Conclusions:
- Mast cell degranulation is implicated in the pathogenesis of skin fibrosis in the tight-skin mouse model.
- Ketotifen shows therapeutic potential for managing skin fibrosis and related mast cell activity in scleroderma.