A 21-aminosteroid inhibits stimulated monocyte hydrogen peroxide and chemiluminescence measurements from MS patients and controls.
Monocytes are recruited to active sites of multiple sclerosis (MS) demyelination and may promote local tissue injury by generating an inflammatory response, mediated in part by the production of toxic oxygen metabolites. Corticosteroids are frequently and effectively used to ameliorate MS exacerbations, despite inadequate knowledge about the mechanism. We assessed the effects of a 21-aminosteroid, U74500A, a new class of steroid derivatives without glucocorticoid or mineralocorticoid effects, on the production of hydrogen peroxide (H2O2) and chemiluminescence by stimulated monocytes harvested from 8 stable MS patients and age- and sex-matched controls. H2O2 measurements and chemiluminescence were significantly reduced in both groups by U74500A. These results demonstrate that 21-aminosteroids reduce production of toxic oxygen metabolites by monocytes and thus their inflammatory potential, suggesting that these agents may be potentially effective and safe treatment for MS exacerbations.
Fisher
M
M
Department of Neurology, Medical Center of Central Massachusetts-Memorial, Worcester 01605.
Levine
P H
PH
Doyle
E M
EM
Arpano
M M
MM
Bergeron
D A
DA
Cohen
R A
RA
Hoogasian
J J
JJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D009103:Multiple Sclerosis / Q000097:blood*; D009994:Osmolar Concentration; D011281:Pregnatrienes / Q000494:pharmacology*; D012016:Reference Values
D011281:Pregnatrienes; D006861:Hydrogen Peroxide; C053356:U 74500A