Early markers for protective mechanisms during rush venom immunotherapy

Background: Allergen-specific venom immunotherapy (VIT) represents the only rational-based option to treat allergic sensitizations against bee and wasp venom. So far, there is not much knowledge about early induction of protective and tolerogenic pathways during VIT. Objectives: To identify the earliest markers for protective mechanisms against allergic reactions in the peripheral blood during the build-up phase of VIT. Methods: PBMC and monocytes were isolated, and serum samples were taken before and during a five day build-up phase from 65 hymenoptera venom allergic patients. Expression level of tolerogenic markers was analyzed on mRNA and protein level. Serum levels of different soluble tolerogenic factors were measured. Results: We observed significantly enhanced tryptophan degradation, elevated ILT4 expression of monocytes as well as IL-10 production of CD3(+) T cells only a few hours after the first injection on day 1, followed by increased IL-10 serum levels, monocyte apoptosis and elevated intracellular cAMP levels of monocytes on day 3 combined with a higher ILT3 protein expression and IL-10 secretion of monocytes on day 5. Conclusion: From these data, we conclude that tryptophan depletion, ILT3/4-mediated inhibition, higher IL-10 production as well as intracellular cAMP might contribute to early induction of protective mechanisms against allergic reactions during the build-up phase of VIT.