Differential effects of proclatic upon activation and differentiation of human B lymphocytes

doi:10.1016/0165-5728(93)90282-4

Journal of Neuroimmunology

Volume 47, Issue 1, August 1993, Pages 35-40

https://doi.org/10.1016/0165-5728(93)90282-4 Get rights and content

Abstract

The effects of human prolactin on enriched peripheral B lymphocytes obtained from healthy males were examined. Immunoregulation by prolactin was studied in B cells activated with either anti-IgM alone, or anti-IgM antibodies and recombinant interleukin-2 (r-IL-2), as well as control resting B cells. Expression of IL-2 receptors (IL-2R), and IgM and IgG in the culture supernatants were used as a measure of B cell activation and differentiation. Prolactin significantly synergized with IL-2 in the enhancement of surface expression of IL-2R on anti-IgM treated B cells. Although no differentiating effect was observed on resting B cells, prolactin (0.2–100 ng/ml) exhibited a dose-dependent enhancement upon both IgM and IgG secretion from B cells treated with anti-IgM and IL-2. In the absence of exogenously added IL-2 similar differentiating effect were observed in B cells treated with anti-IgM at prolactin concentrations of 0.2–10 ng/ml, but not 100 ng/ml. Thus, the present results demonstrate the modulatory effect of prolactin on activation and differentiation of anti-IgM triggered human B cells, and emphasize the importance of co-stimulatory signal mediated by IL-2 in B cell responses to high prolactin levels. These findings extend the immunoregulatory effects of prolactin, previously confirmed for T cells, to the B cell arm of the immune response, and suggest an important role of prolactin in mediating adaptation and communication between the nerve and immune systems.

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Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal homeostasis has great influence in achieving competent and healthy immune system function. Prolactin has a bioactive function acting as a hormone and a cytokine. It influences the immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Hyperprolactinemia has been detected in many patients with different autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, multiple sclerosis, autoimmune thyroid disease, systemic sclerosis, among others, and its believed to play a crucial role in disease pathogenesis. A direct correlation between prolactin levels and disease activity was not clear. Genetic factors may have a role in humans as in animal models. Dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, the authors attempt to provide a critical overview on the role of prolactin in the immune system, exploring its contribution to the development of autoimmune diseases.
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The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8⁺ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women.
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2019, Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases
Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal homeostasis has great influence in attaining competent and healthy immune system function. Prolactin has a bioactive function acting as a hormone and a cytokine. It influences the immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Hyperprolactinemia has been detected in many patients with different autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, multiple sclerosis, autoimmune thyroid disease, and systemic sclerosis, among others, and it is believed to play a crucial role in disease pathogenesis. A direct correlation between prolactin levels and disease activity was not clear. Genetic factors may play a role in humans as in animal models. Dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored.
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The etiology of autoimmune diseases is the result of a complex interaction of the immune system with environmental and genetic factors, although the underlying mechanisms are not completely understood. A number of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, show a striking female predominance. Sexual dimorphism in autoimmunity can be explained at least in part by the role of sex hormones in the regulation of the immune system, whose cells express estrogen and androgen receptors. Furthermore, other mechanisms such as epigenetics may be involved in this multifaceted scenario. The rupture of this complex balance may contribute to the development of autoimmune diseases. In this chapter, we will focus on the effects of sex hormones and prolactin on the pathogenesis and development of autoimmunity.
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Inflammation is an immune defense mechanism against injury or infection, and plays an integral role in both the innate and adaptive immune responses. Humans exhibit strong sex differences in immune responses and inflammation, with women having an enhanced immune reaction as compared to males. Sex hormones and genetics play a role in mediating various components of the immune system and contribute significantly to the sex differences observed in the immune response and inflammation. A sustained immune response characterized by the production of autoantibodies or effector immune cells that react to host tissues or endogenous peptide results in autoimmune diseases. Eighty percent of autoimmune disease patients are female. The enhanced immune reactivity in females may predispose women to the development of autoimmune disease and is implicated in the sexual dimorphism of autoimmune disease prevalence. Studies have examined the influence of female and male sex hormones, as well as genetic differences in both sexes that are associated with enhanced risk or prevalence of autoimmune diseases. Investigations have also examined the effect of sex hormone therapy as treatment options for autoimmune diseases. A new area of interest is the contribution of genes on sex and nonsex chromosomes in autoimmune disease prevalence and progression. A better understanding of the mechanisms that underlie development and progression of autoimmune diseases, as well as the mediators of sex differences in these disorders may result in the development of novel therapeutic strategies to better manage these unique disorders.
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Many studies have shown that prolactin (PRL) plays an important role in autoimmune diseases. The aim of this study was to compare the current frequency of autoimmune thyroid disease (ATD) in prolactinomas with another type of functional pituitary adenoma (FPA), somatotrophinoma. Another aim of the study was to evaluate possible factors related to thyroid autoimmunity and the process of ATD in FPAs.
We retrospectively evaluated the presence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) and thyroid morphologic findings in our patients with FPA (78 with acromegaly and 83 with prolactinoma). The relationship of autoantibody positivity with baseline PRL levels, activity of acromegaly, and treatment of dopamine agonists (DA) and hypogonadism was also assessed. Patients with ATD and hypothyroidism due to autoimmune thyroiditis were also evaluated.
ATD (Hashimoto's thyroiditis) was detected more frequently in patients with prolactinoma than in patients with acromegaly (33% and 17%, respectively; p = 0.01). Thyroid autoantibody positivity was found more frequently in females in the whole group (p = 0.02) and in the acromegaly group (p = 0.008). There was no difference according to sex among the patients with prolactinoma (p = 0.800). ATD was found not to be related with baseline PRL levels, treatment of DA, and presence of hypogonadism (p = 0.232, p = 0.435, p = 0.464, respectively) in the prolactinoma group, and activity of acromegaly, presence of hypogonadism in the acromegaly group (p = 0.753, p = 0.654, respectively). Autoimmune hypothyroidism was more frequent in the prolactinoma group than in the acromegaly group among patients with thyroid autoantibody positivity (p = 0.004).
Thyroid autoantibodies should be evaluated both at the time of diagnosis and during the course of treatment in patients with prolactinoma, and thyroid function tests should be closely monitored in patients with autoantibody positivity.

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Differential effects of proclatic upon activation and differentiation of human B lymphocytes

Abstract

Am. J. Med. Sci.

Immunopharmacology

Immunopharmacology

Suppression of macrophage activation and T lymphocyte function in hypoprolactinemic mice

Science

Analysis of risk factors for acute allograft rejection after heart transplantation

J. Heart Transplant.

Effects of calcitonin gene related peptide, Neurokinin A on the mitogenic response of human peripheral blood mononuclear cells

Naunyn-Schmiedeberg's Arch. Pharmacol.

Nervous system-Immune system interactions

Regulation of IL-2 driven T lymphocyte proliferation by prolactin

Requirment of nuclear prolactin for IL-2 stimulated proliferation of T lymphocytes

Science

A human lymphoblastoid cell line produced prolactin

Endocrinology

Defective low density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B-cells

Clin. Exp. Immunol.

Human B lymphocyte function; cell triggering and immunoregulation

J. Infect. Dis.

Lymphoid tumor cells as models for studies of prolactin gene regulation and action

Prog. Neurol. Endocrin. Immunol.

Prolactin and growth hormone in the regulation of the immune system

PSEBM

Mediators of communication and adaptation in the neuroendocrine and immune systems

FASEB J.

Prolactin as a modulator of lymphocyte responsiveness provides a possible mechanism of action for cyclosporine

Inhibition of lymphocyte proliferation by antibodies to prolactin

FASEB J.