Acute and chronic neuroendocrine effects of interferon-beta 1a in multiple sclerosis.
OBJECTIVE
Treatment of multiple sclerosis with interferon-beta (IFN-beta) results in variable responses interindividually. Cytokine-hormone interactions may modulate the therapeutic effects of IFN-beta. Since hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and other neuroendorine disturbances occur in multiple sclerosis, we determined the detailed neuroendocrine response of patients with multiple sclerosis to IFN-beta.


METHODS
Longitudinal open-label study.


METHODS
Eight patients with relapsing-remitting multiple sclerosis (four women, age 31.9 +/- 1.5 years, EDSS 1.5-2.5).


METHODS
Plasma ACTH, cortisol, prolactin, GH, TSH, LH and FSH were determined in 30-min intervals during 8 h on four occasions: after intramuscular injection of saline; after the first dose of IFN-beta 1a; after the second IFN-beta dose with oral indomethacin pretreatment; and after 3 months of IFN-beta therapy. Dexamethasone-corticotropin-releasing hormone test was performed before and at 3 months on IFN-beta.


RESULTS
Compared to saline, IFN injection resulted in marked rise in plasma ACTH (mean, 370% of baseline), cortisol (214%), prolactin (253%) and GH (756%), between 2 and 6 h after injection. With indomethacin, hormone secretion occurred with reduced peak values. Endocrine response adapted partially after 3 months of treatment. HPA axis activity decreased in most patients, but increased in one patient with frequent relapses.


CONCLUSIONS
Marked neuroendocrine effects occur in response to IFN-beta in multiple sclerosis. Upon prolonged treatment, these effects partially adapt, and HPA axis hyperactivity is reduced. Prospective studies to determine the relation to individual treatment response can be based on these findings.
Then Bergh
Florian
F
Max Planck Institute of Psychiatry, Section of Neurology, Kraepelinstrasse 10, 80804 München, Germany. thenberf@medizin.uni-leipzig.de
Kümpfel
Tania
T
Yassouridis
Alexander
A
Lechner
Christian
C
Holsboer
Florian
F
Trenkwalder
Claudia
C
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D003907:Dexamethasone; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005938:Glucocorticoids; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D013972:Thyrotropin / Q000097:blood
D005938:Glucocorticoids; D016899:Interferon-beta; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D000068556:Interferon beta-1a