Bromocriptine treatment of systemic lupus erythematosus

Walker, Sara E.

doi:10.1191/096120301717165010

Cited by 46 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are in agreement with previous reports studying other hyperprolactinaemic and SLE models, such as reports by McMurray et al [18,31] who showed hyperprolactinaemia induced by pituitary gland transplantation in NZB × NZW mice, and a report by Peeva et al using recombinant PRL to induce hyperprolactinaemia in Sle3/5 R4A-γ2b C57BL/6 mice [32]. Additionally, our data are consistent with several clinical trials showing that a high serum PRL level correlated with SLE disease activity [7,33,34]. …”

Section: Discussionsupporting

confidence: 90%

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

Ledesma-Soto¹,

Blanco-Favéla²,

Fuentes‐Pananá

et al. 2012

BMC Immunol

View full text Add to dashboard Cite

BackgroundProlactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus.ResultsUsing real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor.ConclusionsWe found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.

show abstract

Section: Discussionsupporting

confidence: 90%

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

Ledesma-Soto¹,

Blanco-Favéla²,

Fuentes‐Pananá

et al. 2012

BMC Immunol

View full text Add to dashboard Cite

show abstract

“…Decrease the prolactin in the serum will be another treatment target in SLE. Bromocriptine, a dopamine analog, has been suggested be beneficial in protecting the SLE patients from disease relapse and in reducing the usage of steroid and immunosuppressant by suppressing the circulating prolactin [31]–[33]. Our results showed the therapeutic mechanism of the bromocriptine in SLE and will help us to expand the use of bromocriptine in SLE.…”

Section: Discussionsupporting

confidence: 53%

Multidimensional Single Cell Based STAT Phosphorylation Profiling Identifies a Novel Biosignature for Evaluation of Systemic Lupus Erythematosus Activity

et al. 2011

View full text Add to dashboard Cite

IntroductionDysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE.MethodsPhospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA) patients and 13 healthy donors (HDs). A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10) were also monitored.ResultsWe observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF), and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells.ConclusionsThe basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE.

show abstract

“…While a relationship between disease activity and prolactin level has not been clearly established in human SLE, antibodies to prolactin appear to correlate with lower disease activity [39]. Small clinical trials in SLE patients suggest a therapeutic effect of bromocriptine, but large scale, definitive trials have not been performed [40–42]. Administration of prolactin to NZB/W mice accelerates disease while treatment with bromocriptine, a drug that inhibits prolactin secretion, can retard disease progression [43].…”

Section: Introductionmentioning

confidence: 99%

Hormonal milieu at time of B cell activation controls duration of autoantibody response

Jeganathan

Peeva

Diamond

2014

Journal of Autoimmunity

View full text Add to dashboard Cite

A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in transgene-expressing B cells and elevated serum titers of anti-DNA antibodies. We previously demonstrated that autoreactive B cells maturing in an estrogenic milieu develop as marginal zone (MZ) B cells; when these same B cells mature in the presence of increased prolactin, they develop as follicular (Fo) B cells. To determine the long term consequence of this differential maturation of DNA-reactive B cells, we treated R4Atg BALB/c mice with E2 or Pr for 6 weeks until serum titers of anti-DNA antibody were high, at which time hormonal exposure was discontinued. In E2-treated mice, the anti-DNA titers remained high even 3 months after discontinuation of hormone exposure. Nascent B cells underwent normal tolerance induction, but existing autoreactive MZ B cells persisted and continued to secrete autoantibody. In contrast, Pr caused only a short-term increase in anti-DNA antibody titers. By 3 months after cessation of hormone treatment, serum anti-DNA antibody titers and B cell subsets were indistinguishable from those in placebo (P) treated mice. These findings suggest that autoantibody responses are sustained for variable lengths of time depending on the B cell subset producing the autoantibodies. This observation may be relevant to understanding the heterogeneous presentation of patients with SLE and to the design of therapies targeting speci?c B-cell populations in autoimmune disease.

show abstract

Bromocriptine treatment of systemic lupus erythematosus

Cited by 46 publications

References 44 publications

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

Multidimensional Single Cell Based STAT Phosphorylation Profiling Identifies a Novel Biosignature for Evaluation of Systemic Lupus Erythematosus Activity

Hormonal milieu at time of B cell activation controls duration of autoantibody response

Contact Info

Product

Resources

About