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.


OBJECTIVE
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.


CONCLUSIONS
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.
Bussmann
C
C
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Xia
J
J
Allam
J-P
JP
Maintz
L
L
Bieber
T
T
Novak
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001514:Bee Venoms / Q000276:immunology* / Q000627:therapeutic use*; D002469:Cell Separation; D003888:Desensitization, Immunologic; D053222:Fas Ligand Protein / Q000097:blood / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D014862:Wasp Venoms / Q000276:immunology* / Q000627:therapeutic use*; D055815:Young Adult
D001514:Bee Venoms; D053222:Fas Ligand Protein; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014862:Wasp Venoms; D016753:Interleukin-10