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other·preclinical research, biomedical research, immunology, rheumatology, dry eye·PMC10448398

A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse model

JADA Foundational Science · 6 authors, 4 centres

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Mice were treated for 8 weeks with either vehicle control, high-dose dexamethasone alone, aspirin-triggered resolvin D1 alone, or a combination of low-dose dexamethasone with aspirin-triggered resolvin D1. The authors conclude the combination is effective and may be suitable for long-term administration due to reduced adverse effects compared to high-dose dexamethasone. Limitations include the lack of experiments directly proving lymphocytic infiltration causes glandular dysfunction and the need for future dose-response studies to find the minimum effective dexamethasone dose.

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preclinical research

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ORIGINAL PAPER

PMC10448398

A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse model

JADA Foundational Science

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ABSTRACT

Abstract Background Sjögren syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and diminished secretory function of the salivary glands. Dexamethasone (DEX) resolves dry mouth and lymphocytic infiltration; however, this treatment is difficult to maintain because of multiple adverse effects (eg, osteoporosis and skin thinning); likewise, aspirin-triggered resolvin D1 (AT-RvD1) increases saliva secretion but cannot eliminate lymphocytic infiltration. Previous studies showed that a combination of low-dose DEX with AT-RvD1 before disease onset prevents SS-like features in a mouse model; however, this is not clinically practical because there are no reliable indicators of SS before disease onset. Therefore, the authors applied the combined treatment at disease onset to show its efficacy and comparative lack of adverse effects, so that it may reasonably be maintained over a patient’s lifetime. Methods NOD/ShiLtJ mice were treated with ethanol (vehicle control), high-dose DEX alone, AT-RvD1 alone, or a combination of low-dose DEX with AT-RvD1 at disease onset for 8 weeks. Then saliva flow rates were measured, and submandibular glands were harvested for histologic analyses. Results A combined treatment of low-dose DEX with AT-RvD1 significantly decreased mast cell degranulation and lymphocytic infiltration, increased saliva secretion, and restored apical aquaporin-5 expression in submandibular glands of NOD/ShiLtJ mice. Conclusions Low-dose DEX combined with AT-RvD1 reduces the severity of SS-like manifestation and prevents the development of advanced and potentially irreversible damage, all in a form that can reasonably be administered indefinitely without the need to cease treatment because of secondary effects. Key Words: Salivary glands, inflammation, resolvins, steroids, lipid mediators

CITATION EXPORT

Harim Tavares dos Santos, Frank Maslow, Kihoon Nam et al.. A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse model. JADA Foundational Science. (2022). https://doi.org/10.1016/j.jfscie.2022.100016

AUTHORS

6 · 4 CENTRES

Harim Tavares dos Santos, Frank Maslow, Kihoon Nam, Bryan Trump, Gary A Weisman, Olga J Baker

aDepartment of Otolaryngology, Head and Neck Surgery, University of Missouri, Columbia, MO
bChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO
cSchool of Dentistry and Department of Dermatology, University of Utah, Salt Lake City, UT
dDepartment of Biochemistry, University of Missouri, Columbia, MO