ABSTRACT
Interleukin (IL)-12 is a cytokine thought to play a major role in the pathogenesis of multiple sclerosis (MS). We have previously shown that patients with progressive MS have a high percentage of IL-12-producing monocytes in the blood compared to normal individuals. We analyzed 269 blood samples from 189 MS patients for the percentage of IL-12-producing monocytes. We found that the increased IL-12 expression correlates with disability, as measured by the Expanded Disability Status Scale (EDSS), and with disease activity, measured by the presence of gadolinium-enhancing magnetic resonance imaging (MRI) lesions.
Subject(s)
Interleukin-12/blood , Magnetic Resonance Imaging , Monocytes/metabolism , Multiple Sclerosis/blood , Multiple Sclerosis/diagnosis , Adult , Aged , Female , Humans , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/physiopathology , Severity of Illness IndexABSTRACT
IL-12 is a key cytokine for Th1 cell development and may be important in the pathogenesis of multiple sclerosis (MS). The beta2-agonist salbutamol is known to decrease IL-12 production in monocytes of normal individuals through increased intracellular cAMP. In a prospective open-label study, we investigated by flow cytometry the effect of a 2-week long oral salbutamol treatment on monocyte IL-12 production in 21 secondary progressive MS patients. Baseline IL-12 production was higher in patients than in healthy controls. The treatment induced a significant decrease in the percentage of IL-12-producing monocytes and dendritic cells that lasted up to 1 week after treatment interruption. This first report on the use of salbutamol in MS shows that this drug has immunomodulatory properties both in vivo and in vitro, and may be beneficial in the treatment of MS.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Albuterol/pharmacology , Interleukin-12/biosynthesis , Multiple Sclerosis/drug therapy , Administration, Oral , Adolescent , Adult , Albuterol/administration & dosage , Albuterol/therapeutic use , B7-1 Antigen/biosynthesis , Bucladesine/pharmacology , CD40 Antigens/biosynthesis , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Female , Humans , Lipopolysaccharides/pharmacology , Male , Middle Aged , Monocytes/drug effects , Monocytes/metabolism , Multiple Sclerosis/immunologyABSTRACT
Selective deprotection of peracetylaucubin (3) by use of KCN led to 6-O-acetylaucubin (4), which was readily converted into 2',3',4',6', 10-penta-O-benzoylaucubin (7). Configuration inversion performed on 7, using a modified Mitsunobu reaction, followed by deprotection, afforded 6-epi-aucubin (2).