Opportunities and challenges: interleukin-22 comprehensively regulates polycystic ovary syndrome from metabolic and immune aspects

Abstract

Polycystic ovary syndrome (PCOS) is known as a prevalent but complicated gynecologic disease throughout the reproductive period. Typically, it is characterized by phenotypic manifestations of hyperandrogenism, polycystic ovary morphology, and persistent anovulation. For now, the therapeutic modality of PCOS is still a formidable challenge. Metabolic aberrations and immune challenge of chronic low-grade inflammatory state are significant in PCOS individuals. Recently, interleukin-22 (IL-22) has been shown to be therapeutically effective in immunological dysfunction and metabolic diseases, which suggests a role in the treatment of PCOS. In this review, we outline the potential mechanisms and limitations of IL-22 therapy in PCOS-related metabolic disorders including its regulation of insulin resistance, gut barrier, systemic inflammation, and hepatic steatosis to generate insights into developing novel strategies in clinical practice.

Interlukin-22 improves ovarian function in polycystic ovary syndrome independent of metabolic regulation: a mouse-based experimental study

“…In previous studies, although many types of PCOS animal models have been used, due to the unidentified aetiology and complex pathogenesis of PCOS, none of them could simulate the phenotypes of PCOS patients without metabolic disorders [ 17 ]. In addition, IL-22 plays an important role in alleviating the metabolic syndrome by improving insulin resistance [ 11 ]. Specifically, IL-22 restores insulin secretion in obese mice by protecting pancreatic beta cells from oxidative and endoplasmic reticulum stress [ 7 , 8 ].…”

“…However the limitation of our study is that it is still validated in animal models, and since IL-22 is an inflammatory factor with a wide range of actions throughout the body, which may not play the same role in different organs and models. In addition, there is no conclusive evidence on the dosage and safety of IL-22 [ 11 ]. Thus our study provides further support for the exploration of IL-22 for the treatment of non-metabolic PCOS.…”

“…In addition, serum levels of IL-22 have been associated to some extent with obesity, although research findings vary [ 7 , 9 , 10 ]. Thus research into IL-22 function has triggered a new surge in endocrine metabolic disorders [ 11 , 12 ]. Regardless, due to the extensive chronic low-grade inflammatory response in PCOS, IL-22 has been reported by many studies to alleviate PCOS by improving systemic inflammation levels as well as insulin resistance [ 13 , 14 ].…”