Prolactin in multiple sclerosis

Abstract

Multiple sclerosis (MS) is more common among women than men. MS often goes into remission during pregnancy, when prolactin (PRL) levels are known to be high. In an animal model of demyelination, PRL promoted myelin repair, suggesting it has potential as a remyelinating therapy in MS. In this systematic review, we examined the known associations between PRL and MS, in order to elucidate its potential role in the pathophysiology and treatment of MS. A systematic search was performed in the electronic databases PubMed and EMBASE, using the keywords "prolactin" AND "multiple sclerosis." The inclusion criteria were met by 23 studies. These studies suggested to us that elevated PRL may be more common in MS patients than in controls. Hyperprolactinemia may also be associated with clinical relapse in MS, especially among patients with hypothalamic lesions or optic neuritis; however, it is unknown if this is a cause or consequence of a relapse. Overall, most people with MS have normal PRL levels. The impact of PRL on MS outcomes remains unclear.

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

“…For example, physiological concentrations of PRL (<0.02 μg/ml) are more effective than high PRL levels (0.1 μg/ml) in stimulating antibody production by SLE lymphocytes (64), low PRL levels stimulate and high levels inhibit NK cell proliferation (65), and hyperprolactinemic patients (mean serum PRL of 0.98 μg/ml or 0.20 μg/ml) show reduced NK cell numbers (66) and function (67). Also, hyperprolactinemia protects against inflammatory arthritis in rats (present study), and treatment with a high, but not a low, dose of PRL exacerbates experimental MS (61). In the latter, however, the low dose of PRL is beneficial when combined with IFN-β, and Prlr -/-mice display a significantly worse outcome than wild-type mice (61).…”

“…Also, hyperprolactinemia protects against inflammatory arthritis in rats (present study), and treatment with a high, but not a low, dose of PRL exacerbates experimental MS (61). In the latter, however, the low dose of PRL is beneficial when combined with IFN-β, and Prlr -/-mice display a significantly worse outcome than wild-type mice (61). The variability of the relationship between PRL and autoimmune diseases is further highlighted under physiological hyperprolactinemia.…”

“…Although the role of endogenous PRL in autoimmune diseases has generated controversies (57)(58)(59)(60)(61)(62)73), our study reveals that elevating serum PRL levels significantly attenuates cartilage death and joint inflammation in inflammatory arthritis. This strategy may be comparable to the well-established use of glucocorticoids in patients with RA, in which levels of the endogenous hormones appear insufficient to control the disease (74).…”

“…A large body of literature has focused on PRL having a pathogenic role in RA and also in other autoimmune diseases, like SLE, Sjögren's syndrome, Hashimoto's thyroiditis, celiac disease, MS, etc. Its pathogenic role is largely based on the preponderance of autoimmune diseases in women (56) and on PRL being a sex-linked hormone, on the higher levels of circulating PRL detected in some patients (6%-45%, depending on the disease and specific study), on the therapeutic effects of the dopamine agonist bromocriptine, and on the immunoenhancing properties of PRL (57)(58)(59)(60)(61). However, in RA, as in the other autoimmune diseases, treatment with bromocriptine is not always effective and the association between PRL levels Bax, and p53 mRNA levels in ankle joints from PRL-treated and nontreated rats on day 21 after CFA (n = 3-8).…”

“…Bars represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. and disease activity has been inconsistent (58)(59)(60)(61)(62). Generalizations are confounded by the contribution of PRL synthesized locally by cells like chondrocytes (12), synoviocytes and immune cells (16), and endothelial cells (63), which can potentiate the action of systemic PRL.…”