Acute and chronic neuroendocrine effects of interferon-beta 1a in multiple sclerosis.

Summary Objective  Treatment of multiple sclerosis with interferon-β (IFN-β) results in variable responses interindividually. Cytokine–hormone interactions may modulate the therapeutic effects of IFN-β. 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-β. Design  Longitudinal open-label study. Patients  Eight patients with relapsing-remitting multiple sclerosis (four women, age 31·9 ± 1·5 years, EDSS 1·5–2·5). Measurements  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-β 1a; after the second IFN-β dose with oral indomethacin pretreatment; and after 3 months of IFN-β therapy. Dexamethasone–corticotropin-releasing hormone test was performed before and at 3 months on IFN-β. 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-β 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.