Bromocriptine suppresses postpartum exacerbation of collagen‐induced arthritis

Abstract

We administered bromocriptine (Parlodel) to arthritic mice immediately postpartum, and found that the drug suppressed the clinical exacerbation of joint involvement that was seen in untreated animals. Approximately 50% reduction in severity of disease was achieved with bromocriptine (P < 0.001). The effect may be due to suppression of the prolactin release that normally occurs postpartum.Immunization of susceptible strains of mice with heterologous type I1 collagen leads to a disease which causes pathologic changes in the joints that are similar to those that occur in humans with rheumatoid arthritis (1). We have shown that in D B N l mice, there is a remission of this disease during gestation and an exacerbation after parturition (2). Parturition is associated with many hormonal changes, one of the more significant of which is a decrease in the circulating levels of progesterone. The resulting increase in prolactin levels may be involved in the postpartum exacerbation of symptoms of collageninduced arthritis.Bromocriptine, a dopaminergic-receptor stimulant, is prescribed for the control of hyperprolactinemia in cases of hypogonadism and/or galactorrhea, and for the suppression of puerperal lactation. We tested its effect in mice with collagen-induced arthritis after they had given birth. MATERIALS AND METHODSNine-week-old female DBN1 mice (Olac, Bicester, UK) were injected intradermally with 100 pg of bovine type I1 collagen in Freund's complete adjuvant. An intraperitoneal injection of 100 pg of type I1 collagen in 0.1M acetic acid was administered 3 weeks later (2). Syngeneic matings resulted in pregnancies 4-8 weeks after the primary immunizations.At parturition, the mice were randomly assigned to either the treatment group or the control group (12 animals per group). The treatment group was given daily subcutaneous injections of 0.1 mg (approximately 5 mglkg of body weight) of bromocriptine (Parlodel; Sandoz, Middlesex, England) dissolved in ethanokwater (100 pl), 1: 1 volume/volume, over 5 days, commencing on the day the mice gave birth. Mice in the control group received 100 pl of the ethanokwater vehicle only.The severity of arthritis was assessed in individual mice by use of a clinical scoring system (0-4 per limb; maximum score 16) (2). RESULTSThe mean clinical scores in both groups of mice with collagen-induced arthritis are presented in Figure 1. There was an increase in the mean clinical scores in both groups of mice after parturition. However, in the mice given bromocriptine injections, the increased

Pathogenesis of Degenerative Joint Disease in the Human Temporomandibular Joint

“…On the other hand, testosterone may inhibit the release of these cytokines from stimulated monocytes (Li etal, 1993). In addition, prolactin, released from the pituitary in response to estrogen, exacerbates collagen-induced arthritis in mice (Whyte and Williams, 1988). Prolactin also stimulates cytokine production by lymphocytes and macrophages.…”

“…Prolactin also stimulates cytokine production by lymphocytes and macrophages. Bromocriptine, a dopaminergic agonist that inhibits prolactin release from the pituitary, markedly (50%) suppresses the severity of collagen-induced arthritis in post partum (i.e., hyperprolactinemic) mice (Whyte and Williams, 1988). Sex hormone regulation of cytokine production is complex and may be dependent on other co-existing factors.…”

Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes.

“…From mixed in vivo/in vitro experiments, treatment of mice with bromocryptine has been found to suppress mixed lymphocyte responses of splenocytes (3) and to inhibit macrophage activation and Tlymphocyte proliferation (4). In clinical studies, bromocryptine has been reported to suppress postpartum exacerbation of collagen-induced arthritis and to alleviate the symptoms of systemic lupus erythematosus (5). Administration of bromocryptine also prevented development of experimental autoimmune diseases in rodents (6,7).…”

Prolactin and Autoimmunity

“…Indeed, severe disease was associated with longer breastfeeding periods and higher number of breast fed children. In animal models, bromocriptine was able to suppress postpartum exacerbation of collagen-induced arthritis (86). In humans, the treatment with bromocriptine revealed controversial findings (87,88), probably because bromocriptine does not influence lymphocyte-derived PRL production (89).…”