Background/Purpose:

Rheumatoid arthritis (RA) is the most common rheumatic disease which mainly affects women. In the last decade, it is known that prolactin (PRL) is a sex hormone with immunomodulatory properties. It has been shown that high prolactin levels are associated with an increase of the disease activity postpartum and that the PRL inhibitor, bromocriptine, improves disease activity of patients with RA. Furthermore, the serum PRL levels correlated positively with the Larsen score.

Recently, the prolactin receptor (PRLR), belonging to the family of cytokine receptors, has been described in atherosclerotic plaques, mainly on macrophages.

The objective of the study is to determine 1) the level of PRL in RA patients related to rheumatoid factor (RF), anti-cylic citrullinated peptide antibodies (ACPA), erosive disease and response to anti-TNF treatment 2) PRLR expression in synovial tissue of RA, psoriatic arthritis (PsA) and osteoarthritis (OA) patients 3) the phenotype of the PRLR expressing cell.

Methods:

Serum prolactin levels were measured using immunofluorescent metric assay in patients with RA before TNF-α blockade (n=101). The expression of PRLR was determined in synovial tissue (ST) of RA (n=91), PsA (n=15) and OA (n=9) patients using digital image analysis. Immunofluorescence (IF) was used to detect the PRLR expressing cell type.

Results:

A trend towards higher PRL levels were found in patients who are rheumatoid factor positive compared to rheumatoid factor negative RA patients (5.0 (2-24) and 7.3 (2.5-36) µg/L; P=0.06). When the PRL levels were divided into 3 categories, the percentage of the RF positive patients had significantly higher PRL levels (P=0.021). A trend towards higher PRL levels were also seen in patients who are ACPA positive (P=0.063) and similar results with erosive disease (P=0.057).   Baseline PRL levels were significantly lower in non-responders (median (range): 5.3 (2.0-22) ug/L)  than in moderate (7.0 (2.5-36)) and responders (8.5 (4.0-19)) on anti-TNF treatment (P=0.025). Overall, the prolactin levels were similar between females and males.

PRLR expression was higher in RA (median (range): 0.055 (0.000-5.673) IOD/nuclei/mm²) and PsA (0.182 (0.000-5.336)) compared to OA (0.000 (0.000-0.908); P=0.024; Fig 1). Using IF, co-localisation was observed with macrophages and endothelial cells. The expression of the PRLR was also confirmed by RT-PCR in macrophages.

Conclusion:

Higher levels of PRL are found in patients who respond to anti-TNF treatment. The expression of the PRLR in synovial tissue, mainly by macrophages, is higher in the inflammatory diseases (RA and PsA) than in OA. Our combined data suggest an important role of prolactin and its receptor in RA.