Author Of 1 Presentation
P0329 - Effects of adrenocorticotropic hormone on melanocortin receptors, regulatory immune cells, and MRI in MS (ID 1915)
Abstract
Background
Background: Adrenocorticotropic hormone (ACTH) is an alternative to corticosteroid therapy to treat relapses in Multiple Sclerosis. ACTH stimulate low levels of corticosteroid release from the adrenal glands, but it also works through the melanocortin system to induce anti-inflammatory, neuroprotective, osteoprotective, and analgesic effects specific to ACTH by binding to melanocortin receptors (MCR). Although cortisol and cortisol receptor levels have been examined extensively in MS, ACTH effects on MCR expression and on regulatory immune cells have not been examined, particularly in patients undergoing MRI-confirmed MS relapses.
Objectives
Objectives: To elucidate if ACTHAR administration causes changes in MRI scans, modifies expression of MCR acutely and long-term in MS, or changes regulatory subsets, acutely or long-term.
Methods
Methods: Six MS patients with acute clinical exacerbations and active contrast-enhancing lesions were given a 10-day course of subcutaneous ACTHAR (80 units/day). Blood was drawn from patients at baseline, 10 days, and 1, 3, 6, and 12 months post ACTHAR injections. MRIs were performed at baseline and months 3, 6, and 12. Mononuclear cells (MNCs) were isolated from the blood using Lympholyte FICOL gradient separation and frozen. MNC were stained for MCRs 1,3, and 5 with newly-developed assays, and for CD8+CD28- and CD4+FOXP3+ regulatory T cells (Tregs) for flow cytometry with a Fortessa 4-15 analyzer.
Results
Results: MCRs, 3>1>5 (%) and 1>3>5 (expression) on MNC at baseline, were highly variable after depot ACTH. CD8 Tregs as % of lymphocytes did not change acutely or long-term. However, CD8+CD28+ cytolytic cells (CTL) decreased at 1 month (8.15%) compared to baseline (14.6%; p=0.046, paired t-test, n = 5). 3/6 patients also had a new T2 and/or contrast-enhancing MRI lesions at month 1.
Conclusions
Conclusions: ACTHAR may decrease potentially MS-toxic CD8 CTLs at 1 month post-administration, due to direct effects or to induction of corticosteroids. There were no clear changes in MCRs and T regulatory populations. A 10-day course of ACTHAR was not enough to completely suppress MRI activity in some of patients at month 1. A longer duration of ACTHAR treatment is probably required for further suppression of MRI activity and greater control of immune cell activity.