Oral Administration of IFN-α is Superior to Subcutaneous Administration of IFN-α in the Suppression of Chronic Relapsing Experimental Autoimmune Encephalomyelitis

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-α for suppression of relapse attacks and compared it to s.c. administered IFN-α 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-α 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-α, as was Con A-induced IL-2 secretion, but s.c. IFN-α did not inhibit the Con A-induced proliferation in spleen cells. Oral IFN-α inhibited the mitogen-induced production of IL-2 and IFN-γ, but s.c. IFN-α increased MT-induced IFN-γ 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.