Metformin as a treatment strategy for sjögren’s syndrome

Abstract

Sjögren’s syndrome (SS), a chronic inflammatory disease involving the salivary and lacri-mal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and mus-culoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first‐line agent for type 2 diabetes and has anti‐in-flammatory potential. Its immunomodulatory capacity is exerted via activation of 5’ adenosine monophosphate‐activated protein kinase (AMPK). Metformin inhibits mitochondrial respiratory chain complex I which leads to change in adenosine mono‐phosphate (AMP) to adenosine tri‐phos-phate (ATP) ratio. This results in AMPK activation and causes inhibition of mammalian target of rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR deficient T cells differentiate into regulatory T cells. In this manner, metformin enhances immunoregulatory response in an individual. mTOR is responsible for B cell proliferation and germinal center (GC) differentiation. Thus, reduction of B cell differentiation into antibody‐producing plasma cells occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, metformin has been considered as a treatment strategy and is expected to ameliorate salivary gland function.