Title

Inhibition of inflammatory cell-mediated myelin oxidation and interleukin-1 beta generation by a 21-aminosteroid, U74500A

UMMS Affiliation

Department of Neurology

Date

11-1-1993

Document Type

Article

Subjects

Animals; Antioxidants; Brain Chemistry; Centrifugation, Density Gradient; Electrophoresis, Polyacrylamide Gel; Inflammation; Interleukin-1; Monocytes; Myelin Proteins; Myelin Sheath; Neutrophils; Oxidation-Reduction; Pregnatrienes; Rats; Rats, Sprague-Dawley

Disciplines

Nervous System Diseases | Neurology

Abstract

Inflammatory cell-mediated myelin injury may be an important cause of tissue damage in both acute and chronic central nervous system (CNS) disorders. The 21-aminosteroids are novel derivatives of methylprednisolone without obvious glucocorticoid or mineralocorticoid side effects. We evaluated the ability of 21-aminosteroid, U74500A, to inhibit oxidation of rat brain myelin by human polymorphonuclear leukocytes (PMN) and monocytes. Myelin samples, as confirmed by SDS-PAGE, were incubated with PMN or monocytes and 100 microM U74500A or vehicle. Myelin oxidation by both PMN and monocytes was significantly reduced by U74500A. These observations demonstrate that U74500A can inhibit myelin oxidation by inflammatory cells. Additionally, 100 microM U74500A significantly reduced production of interleukin 1-beta by monocytes exposed to myelin. The aminosteroids may be beneficial in CNS disorders where myelin injury by inflammatory cells appears to contribute, such as acute focal ischemia or multiple sclerosis.

Rights and Permissions

Citation: J Neurol Sci. 1993 Nov;119(2):189-94.

Related Resources

Link to article in PubMed

PubMed ID

8277334