A review of the effects of prolactin hormone and cytokine on the development and pathogenesis of autoimmune diseases

Česká verzia

Authors: M. Fojtíková ¹; M. Černá ²; K. Pavelka ¹
Authors place of work: Revmatologický ústav Praha, ředitel prof. MU Dr. Karel Pavelka, DrSc. ¹; Ústav obecné biologie a genetiky 3. lékařské fakulty UK Praha, přednostka doc. MU Dr. Marie Černá, CSc. ²
Published in the journal: Vnitř Lék 2010; 56(5): 402-413
Category: Reviews

Summary

Prolactin (PRL) is not only a pituitary hormone with important role in the reproduction but it also acts as a cytokine involved in the immune response. Prolactin is produced by many immune system cells that express the prolactin receptor (PRL‑R). PRL is then able to affect local microenvironment of the immune system organs and contribute to maturation as well as functioning of the immune system cells. The role of PRL in the immune reactions is stimulating; its presence significantly increases the ability of the immune cells to proliferate and produce cytokines such as TNF‑α, IFN‑γ, IL‑12, IL‑1β. This effect results from activation of a number of intracellular pathways (Jak2/ STAT, Ras/Raf/MAPK etc.) and activation of the genes linked to apoptosis and proliferation (Bcl‑XL, Bcl‑2, pim, XIAP) or transcription factors (IRF‑1). Interestingly, PRL itself is unable to initiate an immune reaction; it is more a factor maintaining balance within immune reactions, contra‑ regulatory to glucocorticoids, which effect is manifested under critical circumstances of physical or psychological stress. Intensified immunosuppression during stress, combined with a lack of prolactin, has surprisingly been identified during experiments on mice and is also found in human medicine. On the other hand, increased prolactin serum levels were described in several systemic as well as organ‑ specific autoimmune diseases. PRL levels elevation in these diseases might result from several factors: an increased release of prolactin from the anterior pituitary due to inflammatory cytokines or reduced production of suppressive dopamine, or, alternatively, an increased production of prolactin in immune system cells. In some of these diseases, such as celiac disease and systemic lupus erythematosus (SLE), the PRL level correlates with the disease activity. This supports the hypothesis that PRL oversupply shifts the balance in the immune response towards higher activity of the immune system cells and initiation of the immune reaction. For example, in SLE, prolactin prolongs the life cycle of autoreactive B‑lymphocytes and their ability to produce pathogenic autoantibodies. Further research into the effects of PRL and monitoring of patients with hyperprolactinaemia and autoimmune diseases will provide guidance on how to best utilize the possibly so far hidden prolactin potential. It is questionable whether pharmacotherapy could be used to decrease serum PRL levels in the treatment of autoimmune diseases. However, the currently running studies suggest it might be possible to use PRL level detection as a marker of a disease activity.

Key words:
prolactin – autoimmune diseases – cells of the immune system – intracellular pathway – apoptosis – cytokine – stress – disease activity

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