Prolactin and Autoimmunity

Abstract

The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the occurrence of a possible silent LYH in these patients. Finally, the role of anti-prolactinemic drugs to inactivate the immune process in LYH is still discussed.

Favorable Effect of Bromocriptine and Pentoxifylline in Mild Graves Disease Orbitopathy: A Randomized, Open, Clinical Trial

“…In OD from 20 [18][19][20][21] to 18 [16][17][18] mm (p= 0.006), and in OS from 20 [19][20] to 18 [16][17][18] mm (p= 0.006). Proptosis also decreased with PTX treatment; however, this was significant only in OS.…”

“…Proptosis also decreased with PTX treatment; however, this was significant only in OS. In OD decreased from 19 [17.5-19] to 16.5 [16][17][18][19] mm (p= 0.120) and in OS from 19 [17.5-19] to 17 [16][17][18][19][20] mm (p= 0.025). In contrast, the group treated only with MTZ showed no change in proptosis.…”

“…In contrast, the group treated only with MTZ showed no change in proptosis. In OD from 19 [18][19][20] to 19 [16.5-19] mm (p= 0.173), and in OS from 18 [16][17][18][19] to 18 [16][17][18][19][20] mm (p= 0.942). These results are depicted in figure 2.…”

“…However, there is evidence of an association between PRL levels and autoimmune disease. Reduction of PRL causes a decline of interferon gamma and IL-2 secretion by Th1 lymphocytes [20]. A possible mechanism explaining the improvement in GO is its anti-proliferative effect on T lymphocytes by blocking IL-2 production [13,35].…”

“…Lymphocytes and other immune cells express both PRL and the PRL receptor. PRL functions as a local regulator of the lymphocyte proliferation [17,18], increases cytokine production [19] including interferon gamma [20,21], among other immunological effects. Modulation…”