Amelioration of Murine Macrophage Activation Syndrome by Monomethyl Fumarate in Both a Heme Oxygenase 1-Dependent and Heme Oxygenase 1-Independent Manner.

ABSTRACT:

Objective

Macrophage activation syndrome (MAS) is characterized by increased serum levels of ferritin and heme oxygenase 1 (HO-1), and yet no known function is ascribed to these molecules in MAS. Because HO-1 is antiinflammatory, we hypothesized that pharmacologic activation of HO-1 could ameliorate MAS disease activity. Dimethyl fumarate (DMF), a treatment approved by the US Food and Drug Administration for multiple sclerosis, activates HO-1. Monomethyl fumarate (MMF) is the active metabolite of DMF. We therefore evaluated whether MMF could elicit HO-1-dependent therapeutic improvements in a murine model of MAS.

Methods

We induced MAS by repeated activation of Toll-like receptor 9 (TLR-9) in wild-type and myeloid-specific HO-1-deficient mice. MMF was administered twice dail

SUBMITTER: Biswas C 

PROVIDER: S-EPMC8084959 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature