Melanocortin peptides: potential targets in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting in loss of self-tolerance with multiple organs, such as the kidney, skin, joints, and the central nervous system (CNS), being targeted. Numerous immunosuppressant therapies are currently being used for the treatment of SLE, but their clinical utility is somewhat variable because of the clinical heterogeneity. Melanocortins are a family of peptides derived from the common precursor protein pro-opiomelanocortin. These multifunctional peptides activate five subtypes of melanocortin receptors expressed on immune, skin, muscle, bone, and kidney cells and cells within the CNS. Melanocortin peptides have demonstrated a variety of biologic actions including immunomodulation, melanogenesis, and renoprotection. This review aims to introduce the melanocortin system and explore the mechanisms by which they may be beneficial in diseases such as SLE.

Fig. 1

Pro-opiomelanocortin peptide and the post-translational cleavage products [15].

Fig. 2

Potential mechanisms of action of melanocortin peptides in the treatment of systemic lupus erythematosus. Melanocortin peptides may reduce disease activity through multiple potential mechanisms, including the following: systemically induced immunosuppression and anti-inflammation in disease-related target organs and tissues secondary to ACTH-induced steroidogenesis, direct effects of MCR activation on systemically induced immunosuppression and anti-inflammation, including regulation of B and T lymphocytes and macrophages, direct effects of MCR activation on hepatic cells to correct dyslipidemia and possibly reduce accelerated atherosclerosis, direct immunosuppressive and anti-inflammatory effects of MCRs expressed in the epidermis and dermis on chronic cutaneous lesions, direct protective effects of MCR activation on kidney cells particularly podocytes, and direct anti-pyretic and neuroprotective effects of MCRs expressed in the central nervous system and central neurogenic anti-inflammation to reduce inflammation-associated neurologic and psychiatric manifestations [94] (reprinted by permission from Macmillan Publishers Ltd).