Role of Leptin in Autoimmune Diaseases and Malignancy

Leptin is a peptide hormone (16 kDa) secreted mainly by adipocytes, with a variety of physiological roles. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions

1. Leptin influences the neuroendocrine system at several levels, including the hypothalamic-pituitary-adrenal, thyroid, gonadal, and growth hormone axes. However, leptin levels correlated with body mass index (BMI), but not with disease activity. Therefore, it is possible that the interplay between these endocrine systems and the immune response may have influenced, indirectly. Leptin also plays a regulatory role in immunity, inflammation. Although leptin is well known for its regulatory effects on immune cells, its expression and release is reciprocally under the control of different inflammatory stimuli
2. Leptin represents a link between metabolism, nutritional status, and immune responses which is important for optimal functioning of the immune system. Leptin is a cytokine-like hormone with PR inflammatory properties linked to autoimmune diseases. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. Leptin has been shown to enhance immune reactions in autoimmune diseases that are commonly associated with inflammatory responses. Both high and low levels of leptin might contribute to autoimmune diseases. Leptin has been explored as a potential target for therapeutic development in treating autoimmune diseases
3. Moreover, leptin can activate monocytes, dendritic cells and macrophages and stimulate them to produce Th1 type cytokine. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility
4. Leptin stimulates the production of reactive oxygen species
5. Leptin stimulates the release of pro-inflammatory cytokines and prostaglandins
6. One of its functions is the relationship between nutritional status and immune competence
7. It has reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. Leptin also prevents apoptosis of T cells that normally accompanies fasting through up-regulation of anti-apoptotic protein bcl-xL via leptin receptors on lymphocytes. The leptin-induced metabolic pressure sets the basis for an exaggerated immuno-inflammatory response to altered self or non-self, leading to chronic inflammation, metabolic dysregulation, and autoimmunity in subjects with risk factors