Decrease in serum interleukin-21 levels is associated with disease activity improvement in patients with recent-onset rheumatoid arthritis.

Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA.

Elevated prolactin levels in patients with rheumatoid arthritis: association with disease activity and structural damage.

OBJECTIVES: Prolactin (PRL) is a hormone with cytokine-like activities that has been demonstrated to be involved in immune responses. However, there are inconsistent results related to the role of PRL in rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the levels of PRL in serum and synovial fluid in patients with RA and osteoarthritis (OA) and examine whether PRL might be associated with laboratory and clinical disease activity of RA. METHODS: A total of 29 patients with RA and 26 patients with OA were included in the study. The concentration of PRL in the serum and synovial fluid was measured by immunoradiometric assays, and the levels of serum anti-citrullinated protein/peptide autoantibodies (ACPA) and IgM rheumatoid factor (IgM-RF) were analysed by ELISA. Disease activity score (DAS 28) and radiological (Larsen) score were assessed. RESULTS: The levels of PRL in serum (299.55±27.28 vs. 230.59±16.61 mIU/l, p=0.041) as well as in synovial fluid (338.85±33.49 vs. 245.97±21.88 mIU/l, p=0.024) were significantly higher in patients with RA than in patients with OA. A moderate correlation was found between disease activity of RA and levels of PRL in synovial fluid (r=0.485, p=0.010) and the serum PRL levels correlated significantly with the total Larsen score (r=0.484, p=0.014). CONCLUSIONS: The findings of increased prolactin levels in patients with RA lead to the assumption that prolactin may play a role in disease severity and the process of joint damage in RA.

[A review of the effects of prolactin hormone and cytokine on the development and pathogenesis of autoimmune diseases]. / Souborný pohled na efekt hormonu a cytokinu prolaktinu v rozvoji a patogenezi autoimunitních onemocnení.

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-alpha, IFN-gamma, IL-12, IL-1 beta. 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 ofautoimmune diseases. However, the currently running studies suggest it might be possible to use PRL level detection as a marker of a disease activity.

Immunomodulatory role of prolactin in diabetes development.

Pituitary hormone and cytokine prolactin (PRL) is one of the mediators of the bidirectional communication between neuroendocrine and immune systems. It participates in many immunomodulatory activities, affects differentiation and maturation of both, B and T lymphocytes and enhances inflammatory responses and production of immunoglobulins. Hyperprolactinemia has been described in many autoimmune diseases, both systemic (SLE, RA, PsA) and organ-specific (T1D, CD and others) and the activity of PRL has been intensively studied. Nevertheless, no data on PRL contribution to pathogenesis of diabetes mellitus is available, although the effect of PRL on beta cells of the pancreas and insulin secretion has been observed.

[Prolactin response to stress in patients with systemic lupus erythematodes (SLE), rheumatoid arthritis (RA) and in healthy controls]. / Stresová odezva prolaktinu u nemocnych se systémovým lupus erythematodes (SLE), revmatoidní artritidou (RA) a u zdravých kontrol.

Prolactin is a one of the stress hormones, like the growth hormone, ACTH, cortisol and catecholamins. Among its wide range of functions is the important role of controlling the immune response which is, unlike in the case of cortisol, of stimulatory nature. For this activity, it is monitored as a factor influencing the progress and course of autoimmune diseases. The authors of the paper monitored prolactin response to stress in a normal stress situation, i.e. blood collection. A significant difference was detected between the levels of prolactin in 3 successive blood collections in 30 minute intervals (P < 0.001). Prolactin responded by a prompt increase in the serum level, followed by a relatively fast linear decrease. There was no difference in the response between the SLE and RA patient groups and the healthy population. Therefore we conclude that this is a normal reaction of the organism because acute response to stress in patients with autoimmune diseases is the same as in healthy persons.