Prolactin-lnduced Immunoglobulin and Autoantibody Production by Peripheral Blood Mononuclear Cells from Systemic Lupus Erythematosus and Normal Individuals

Abstract

Prolactin (PRL) has been shown to have immunoregulatory effects on a variety of immune responses. Its effect on B cell immune responses is suggested by in vitro data demonstrating a direct effect on B cell activation and differentiation, and also in vivo data demonstrating a biphasic stimulation of antibody production to sheep red blood cells. In addition, it has been shown both in animal models and patients with hyperprolactinemia that PRL may influence the presence of certain autoantibodies. The objective of this work was to study the effect of PRL on the induction of immunoglobulins, and anti-DNA and rheumatoid factor (RF) autoantibody production from peripheral blood mononuclear cells (PBMCs) from normal individuals and systemic lupus erythematosus (SLE) patients. Six female SLE patients and 10 normal individuals (5 females and 5 males) were studied. Ficoll-Hypaque-isolated PBMCs (1×10⁶ cells/ml) with high concentrations of PRL (10^––4––10^––8M) and pokeweed mitogen (PMW) diluted to 1:400. An ELISA assay was used for immunoglobulins, RF and anti-dsDNA antibodies. PRL stimulated IgG and IgM production in a biphasic manner in normal PBMCs. Enhanced synthesis was observed at 10^––6 M, and a stimulatory effect was again observed at higher doses of PRL (10^––4M). In contrast, only a mild stimulatory effect was observed in IgG synthesis by SLE PBMCs. These changes in Ig synthesis, however, did not reach statistical significance. PRL also induced IgG and IgM anti-dsDNA antibodies by both normal and SLE lymphocytes, but no differences were observed when compared to PWM stimulation. PRL induced IgM RF synthesis by normal lymphocytes but had no effect on SLE PBMCs. This study demonstrates that PRL induces immunoglobulin synthesis by normal and to a lesser degree by SLE lymphocytes, and also induces anti-dsDNA antibody by normal and SLE PBMCs, and IgM RF by normal PBMCs. However, the exact mechanism(s) of PRL action on the immune response awaits elucidation.

Big Prolactin 60 kDa is Overexpressed in Salivary Glandular Epithelial Cells from Patients with Sjögren's Syndrome

“…Hyperprolactinemia was reported to be associated, in young women (Ͻ 50 years old), with a higher incidence of autoantibodies, including anti-dsDNA and anti-Ro/SS-A; and in women of Ͼ 50 years, with anti-Ro/SS-A and anti-La/SS-B (Allen et al, 1996). This finding enhanced the hypothesis that PRL may induce the production of autoantibodies (Gutié rrez et al, 1996). Finally, our observation that association between elevated expression of PRL in the salivary acinar cells of SS patients and clinical extraglandular manifestations, which is in agreement with Haga and Rygh (1999), led us to propose that big PRL can be a clinical sign of a more aggressive disease.…”

Hormonal regulation of B-cell function and systemic lupus erythematosus

“…In vitro, PRL stimulates production of IgM, IgG, and anti-dsDNA antibodies as well as IFNγ by PBMCs of lupus patients. [42][43][44] Consequences for clinical consideration While oestrogen clearly influences lupus in mice, [45][46][47][48][49] it is controversial whether it influences disease in humans. Some clinical studies have described a link between oestrogen and disease flares, 50-55 but others failed to show a correlation.…”

Anti-endothelial cell antibodies in the sera of hyperprolactinemic women

“…35 Indeed, it was found that PRL induces the production of IgG and IgM antidsDNA autoantibodies, as well as IgM rheumatoid factor, by lymphocytes derived from normal individuals. 36 It was also found that patients with HPRL of tumoral origin have a higher production of anti-thyroid autoantibodies and an increased B cell population. 37 Thus, the wide spectrum of autoanti-bodies in HPRL patients in our study may represent a non-speci®c stimulation of B lymphocytes, resulting in the production of a broad panel of natural autoantibodies.…”