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INHIBITION OF INDOLEAMINE 2,3-DIOXYGENASE DOES NOT IMPEDE ORAL TOLERANCE
Citation:
BOWMAN, C., M. J. DEVITO, D. G. ROSS, AND M. K. SELGRADE. INHIBITION OF INDOLEAMINE 2,3-DIOXYGENASE DOES NOT IMPEDE ORAL TOLERANCE. Presented at American Academy of Allergy, Asthma and Immunology Annual Meeting 2006, Miami Beach, FL, March 03 - 07, 2006.
Description:
Rationale: Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, regulates immune tolerance through inhibition of T-cell proliferation. Pharmacologic inhibition of IDO, which causes fetal rejection and increased tumor resistance in mice, may prove useful in cancer treatment. IDOs role in tolerance and high levels of expression in the intestine led us to hypothesize that it may function to maintain oral tolerance.
Methods: Initial pharmacokinetic studies were done to achieve relevant levels of the IDO inhibitor 1-methyl-tryptophan (1-MT) during antigen presentation. C3H/HeJ mice were orally treated with 750 mg/kg of 1-MT, a dose previously shown to enhance tumor rejection, and concurrently exposed to a tolerizing dose of ovalbumin (OVA). Experimental groups consisted of: vehicle, 1-MT, vehicle/OVA, or 1-MT/OVA. Following systemic immunization of all groups with OVA and alum, OVA-specific serum IgG and IgE were measured.
Results: Concomitant exposure to OVA and 1-MT did not enhance the subsequent immune response to OVA. Levels of OVA-specific antibody in animals with prior oral exposure to the antigen were reduced by at least half relative to those observed in animals with no prior exposure, regardless of inhibition of IDO.
Conclusions: Transient inhibition of IDO at the time of oral antigen exposure does not prevent induction of oral tolerance. 1-MT does not function as an oral adjuvant under these experimental conditions, and appears unlikely to increase the risk of food allergy. (This abstract does not reflect EPA policy.)