ABSTRACT
BACKGROUND/AIM: Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. METHODS: Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. RESULTS AND CONCLUSION: Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period.
Subject(s)
Hyperprolactinemia/immunology , Hyperprolactinemia/pathology , Inflammation Mediators/administration & dosage , Acute Disease , Animals , Carrageenan/administration & dosage , Chronic Disease , Cold Temperature/adverse effects , Disease Models, Animal , Domperidone/administration & dosage , Edema/chemically induced , Edema/immunology , Edema/pathology , Hyperprolactinemia/chemically induced , Inflammation/chemically induced , Inflammation/immunology , Inflammation/pathology , Male , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/immunology , Prolactin/biosynthesis , Prolactin/metabolism , Rats , Rats, Wistar , Up-Regulation/drug effects , Up-Regulation/immunologyABSTRACT
Reproductive experience (RE), i.e. pregnancy and lactation, induces physiological changes in mammals. Recent data show that neuroimmune interactions are modulated by a diversity of events involving neurotransmitters and neuropeptides. These molecules, particularly dopamine (DA), were reported to mediate the relevant cross talk between immune and neuroendocrine systems. Moreover, DA-mediated regulation of leukocyte function is a reasonable approach to investigate the DA-operated regulatory switch for immune-competent cells, such as macrophages. Therefore, the goals of the present study were to determine the effects of RE on: (1) dopaminergic function through hypothalamic levels of DA, dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA); (2) basal levels of circulating prolactin (PRL); and (3) activity of peritoneal macrophage (phagocytosis and oxidative burst). A total of 16 adult (200-250 g) female Wistar rats were used, divided in two groups: nulliparous and primiparous. Approximately 2-3 weeks after weaning pups from the primiparous group, both groups of rats were tested. The findings indicate that: (1) DOPAC concentrations, DOPAC/DA and HVA+DOPAC/DA ratios decreased in primiparous rats as compared to virgin rats, (2) primiparous rats showed significantly lower serum PRL levels, and (3) phorbol miristate acetate (PMA)-induced oxidative burst was decreased in peritoneal macrophage from primiparous rats as compared to virgin rats. To test the possible positive correlation between serum levels of PRL and the intensity of oxidative burst by peritoneal macrophage, an extra experiment was done with adult virgin female rats treated with domperidone, an antagonist of DA receptors. Domperidone-treated animals showed increased serum levels of PRL and simultaneous increase in peritoneal macrophage oxidative burst. Thus, suggesting an indirect participation of hyperprolactinemia, induced by this treatment in peritoneal macrophage activity of female rats. These results suggest that a previous RE can modulate the activity of dopaminergic hypothalamic systems, while decreasing PRL serum levels and the oxidative burst of peritoneal macrophage. The neurochemical and hormonal RE-induced changes correlate with the immune alterations.
