Faculty Collaboration Database

Oral administration of IFN-alpha is superior to subcutaneous administration of IFN-alpha in the suppression of chronic relapsing experimental autoimmune encephalomyelitis. J Autoimmun 1996 Feb;9(1):11-20

Date

02/01/1996

Pubmed ID

8845048

DOI

10.1006/jaut.1996.0003

Scopus ID

2-s2.0-0029985565 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

We have previously demonstrated that type I IFNs administered orally (p.o.) suppress clinical relapse in murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE), inhibit clinical attacks at doses equivalent to ineffective parenteral (s.c.) doses in acute rat EAE, and decrease the adoptive transfer of EAE. We therefore examined the optimal clinical p.o. dose of murine species-specific IFN-alpha for suppression of relapse attacks and compared it to s.c. administered IFN-alpha in a dose-response experiment in the chronic EAE model. The optimal clinically effective dose for suppression of EAE of p.o. administered murine species-specific IFN-alpha was 10 units and for s.c. administered was 100 units, although the optimal p.o. dose was much more clinically effective than the optimal s.c. dose. Con A- and MT-induced spleen cell proliferation was inhibited by p.o. IFN-alpha, as was Con A-induced IL-2 secretion, but s.c. IFN-alpha did not inhibit the Con A-induced proliferation in spleen cells. Oral IFN-alpha inhibited the mitogen-induced production of IL-2 and IFN-gamma, but s.c. IFN-alpha increased MT-induced IFN-gamma and IL-6 secretion in spleen cells and Con A-induced IL-6 and MT-induced IL-2 and IL-6 in lymph node cells. The oral route is a convenient drug delivery system that may allow the use of lower doses of cytokines and provide enhanced efficacy via unique and potent immunoregulatory circuits without generating additional inflammatory cytokines that may counteract the beneficial effects of s.c. administered type I IFNs.

Author List

Brod SA, Khan M

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Animals
Chronic Disease
Concanavalin A
Encephalomyelitis, Autoimmune, Experimental
Female
Injections, Subcutaneous
Interferon-alpha
Interferon-gamma
Interleukin-2
Interleukin-6
Lymph Nodes
Lymphocyte Activation
Mice
Mice, Inbred Strains
Mycobacterium tuberculosis
Spleen