Effect of Oral Beta Interferon on Subsequent Immune Responsiveness

Abstract

Oral administration of myelin antigens reduces the incidence and severity of EAE in rat and mouse models and decreases the frequency of MBP-reactive cells and the frequency of attacks in some patients with multiple sclerosis. Low-dose oral tolerance has been shown to be mediated by Th2-type regulatory cells that secrete TGFbeta and IL-4/IL-10. Adjuvants and cytokines may modulate oral tolerance. The addition of betaIFN to the experimental therapy regimen, either orally or by intraperitoneal injection, has been shown to enhance the suppressive effects of oral myelin antigens when either are fed the suboptimal dosing regimen to suppress EAE. The current studies were conducted to elucidate the mechanism of the observed in vivo synergy of betaIFN and antigen feeding. Analysis of the in vitro proliferative response and cytokine production by lymphocytes from fed animals in response to specific antigen in culture shows that the synergistic effect may be related to both independent suppression of the immune response by oral betaIFN and enhanced production of TGFbeta and IL-4/IL-10. There was an unexpected increase in the production of gammaIFN by lymphocytes in vitro after three doses of oral betaIFN in vivo. These observations have important implications for the use of cytokines to modulate oral tolerance.

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

“…Large doses of IFN-g given intraperitoneally abrogate oral tolerance (Zhang et al 1990a), anti-IL-12 enhances oral tolerance and is associated both with increased TGF-b production and T cell apoptosis (Marth et al 1996) and subcutaneous administration of IL-12 reverses mucosal tolerance (Eaton et al 2003). Oral IFN-b and IFN-t (tau) synergizes with the induction of oral tolerance in SJL/PLJ mice fed low doses of MBP (Nelson et al 1996;Soos et al 2002). Other exogenous agents which have been reported to enhance oral tolerance when given orally include parasite Ag from H. polygyrus (Shi et al 2000), polysaccharide AZ9 from Klebsiella oxitoca (Sugihara et al 2002) and Schistosoma Mansoni egg antigens (SEA) (Maron et al 1998).…”

Engineered Recombinant Peanut Protein and Heat-Killed Listeria monocytogenes Coadministration Protects Against Peanut-Induced Anaphylaxis in a Murine Model

“…At the present time, there is no satisfactory treatment for PN or other food allergies. Because traditional immunotherapy is not an option for patients with PN allergy (PNA) due to the high incidence of adverse reactions and low rate of maintenance of tolerance (3,4), the only way to manage PNA is by strict dietary avoidance. However, because PN is a hidden ingredient in a number of processed foods, accidental ingestions are common (5,6).…”

“…Allergy to peanuts (PN) 3 accounts for the majority of fatal and near-fatal anaphylactic reactions to food (2), and the incidence appears to be increasing. At the present time, there is no satisfactory treatment for PN or other food allergies.…”

Induction of mucosal tolerance in SLE: A sniff or a sip away from ameliorating lupus?

“…In addition, subcutaneous administration of IL-12 prevents the induction of oral tolerance 91. Oral IFN-γ and IFN-t synergize with the induction of oral tolerance in mice fed low doses of myelin basic protein (MBP) 92–94. Nasal administration of cytokines also enhances tolerance induction and regulatory T cell differentiation.…”