Prolactin and prolactin secretagogues reverse immunosuppression in mice treated with cysteamine, glucocorticoids, or cyclosporin-A.
Suppression of prolactin (PRL) secretion with the dopamine agonist, bromocriptine, has been shown in rodents to diminish a variety of immunologic responses, including delayed type hypersensitivity, primary antibody response, T-cell dependent macrophage activation, and ex vivo T- and B-lymphocyte proliferation in response to mitogens. These same responses can be suppressed by endogenous or exogenous glucocorticosteroids and, in large measure, the immunosuppressant peptide cyclosporin A. The sulfhydryl reducing agent cysteamine (2-aminoethanethiol) is known to reduce pituitary and plasma prolactin levels. Treatment of mice with cysteamine at doses which suppressed circulating PRL levels resulted in suppression of ex vivo blastogenic responses of lymphocytes from treated mice. The T-cell-dependent primary IgM response to immunization with sheep red blood cells was also suppressed by cysteamine treatment. Treatment of mice with drugs stimulating the release of endogenous PRL, or with exogenous ovine PRL, was found to antagonize the suppression of lymphocyte proliferative responses to mitogens induced in mice by glucocorticoid or cyclosporin treatment. These data suggest that many drugs in common clinical use could have potential immunomodulatory actions due to suppression or stimulation of pituitary PRL secretion. Furthermore, lactogenic hormones appear to exert counterregulatory actions which may modify glucocorticosteroid actions on immune and other target issues.
Bernton
E
E
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC.
Bryant
H
H
Holaday
J
J
Dave
J
J
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D003543:Cysteamine / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006462:Hemolytic Plaque Technique; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010546:Perphenazine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
D005938:Glucocorticoids; D001971:Bromocriptine; D003543:Cysteamine; D016572:Cyclosporine; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D010546:Perphenazine; D008787:Metoclopramide; D003345:Corticosterone