Abstract
Experimental autoimmune encephalomyelitis (EAE) is a neuropathological animal model for multiple sclerosis. Antigen-presenting cells (APCs) expressing interleukin-18 receptor (IL-18R) were shown to be crucial in the beginning and progress of EAE. In this study we tested the effect of a novel recombinant immunotoxin targeting IL-18R–bearing APC for EAE prevention. The novel eukaryotic plasmid DT390-IL-18-SRα, encoding recombinant immunotoxin DT390-IL-18, was constructed. The immunotoxin consisted of IL-18 as the targeting moiety, and a truncated diphtheria toxin (DT) as the toxic moiety. Transfection assay and proliferation inhibition assay proved the immunotoxin could be expressed in vitro and was toxic to the activated mouse T cells. To evaluate the preventive effect of DT390-IL-18-SRα on EAE in vivo, cationic liposome-embedded DT390-IL-18-SRα was injected into the hind limbs of EAE mice. DT390-IL-18-SRα–treated mice showed a delayed manifestation of EAE and decreased symptoms compared to the mice treated with plasmid DT390-SRα or phosphate-buffered saline alone. A significant reduction in infiltrating inflammatory cells was detected in the brain tissues from immunotoxin-treated mice as compared with the controls by hematoxylin–eosin staining. This study suggested that the recombinant immunotoxin DT390-IL-18 could be expressed in vitro and in vivo, and prevented murine EAE effectively.
Get full access to this article
View all access options for this article.