Abstract
Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of clinical signs of EAE in Lewis rats.
Highlights
Experimental allergic encephalomyelitis (EAE) is one of best-studied models of autoimmune disease, and is characterized by an autoimmune attack on CNS myelin mediated by neural autoantigen-specific T helper cells [1]
About 10 days after the combined injection of complete Freund adjuvant (CFA) and spinal cord homogenate (SCH), susceptible rats (e.g., Lewis rats) develop a progressive paralysis associated with CNS demyelinization
In experiment 2, 48 male Lewis rats were immunized with SCH plus complete Freund's adjuvant (CFA) mixture, and received daily s.c. injections of bromocriptine (1 mg/kg) or saline (n = 24 each)
Summary
Experimental allergic encephalomyelitis (EAE) is one of best-studied models of autoimmune disease, and is characterized by an autoimmune attack on CNS myelin mediated by neural autoantigen-specific T helper cells [1]. In experiment 1 (left upper and lower panels), 77 male Lewis rats were subjected either to pituitary grafting from littermate donors (n = 39) or to sham operations (n = 38); all were immunized by s.c. injection of a mixture of spinal cord homogenate (SCH) and complete Freund's adjuvant (CFA) as described in Methods. In experiment 2 (right upper and lower panels), 48 male Lewis rats were immunized with SCH plus CFA mixture, and received daily s.c. injections of bromocriptine (1 mg/kg) or saline (n = 24 each). Bromocriptine treatment was very effective in preventing prolactin release at all examined time points (p < 0.001) (Fig. 1, lower right panel) These results indicate that low circulating prolactin levels coincide with absence of clinical signs of EAE in Lewis rats. Contradictory results have been published on the occurrence of hyperprolactinemia in multiple sclerosis patients, with some studies finding increased prolactin levels [22,23,24] while others do not [2527]
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