Chronic low-grade inflammation in polycystic ovary syndrome: is there a (patho)-physiological role for interleukin-1?

The polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women of reproductive age. Its main characteristics are the ovarian overproduction of androgens and ovulatory dysfunction which lead to severe symptoms such as hirsutism, acne, insulin resistance, and infertility. Despite the frequency and disease burden of PCOS, its underlying causes remain unknown, and no causal therapeutic options are available. In recent years, several studies have shown that women with PCOS present with chronic low-grade inflammation indicating an overactivity of the pro-inflammatory cytokine interleukin-1 (IL-1). We show here how IL-1 might affect the ovarian physiology and pathophysiology in animals and humans by reviewing experimental studies on ovarian IL-1 system gene expression and on the effects of exogenous IL-1 on ovarian functions. Although IL-1 ligands and receptors are expressed within the ovarian cells, IL-1 seems to negatively affect the delicate balance between the sex hormones and dominant follicle development, as well as fertility. Whether blockade of the IL-1 signaling leads to an improvement of PCOS-related hormonal abnormalities and symptoms remains to be elucidated in future interventional studies.