title: Cytokine production by peripheral blood mononuclear cells following birch-pollen immunotherapy.
abstract: We studied the Th2/Th1 balance by short-term stimulation of peripheral blood mononuclear cells (PBMC) isolated during the pollen season from seven allergic patients treated with conventional birch-pollen immunotherapy (IT) for 18 months, eight matched allergic control patients and 10 non-atopic individuals. The PBMC were cultured for 7 days with birch-pollen extract (BPE) or tetanus toxoid (TT), and then restimulated with PHA and PMA to induce high IL-5, IL-10 and IFN-gamma production. The serum levels of birch-pollen-specific IgG and IgG4 were significantly elevated after IT treatment. The proliferative response to BPE was significantly enhanced in the allergic control group, but not in the IT-treated group, compared to the non-atopic group (P<0.05). Birch-pollen-specific IL-5 production was significantly enhanced in both the IT-treated group and the allergic control group (P<0.01-0. 05). Furthermore, both the IT-treated group and the allergic control group had a cytokine profile to BPE significantly more Th2 polarized (high IL-5/IFN-gamma ratio) than to TT (P<0.05 and P<0.01, respectively). No differences in IL-10 production between the three study groups were observed. The Th2/Th1 balance in vitro correlated with the serum concentrations of birch-pollen-specific IgE (r=0.60, P<0.05), and in the IT-treated group, also with the IgG and IgG4 levels (r=0.79, P<0.05 and r=0.86, P<0.05, respectively). We conclude that conventional birch-pollen IT does not lead to changes in the cytokine profile of the circulating pool of allergen-specific T cells during birch-pollen season. However, induction of peripheral T-cell tolerance and increased production of specific IgG and IgG4 might be part of the mechanisms of IT.
authors.affiliation: Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.robert.moveare@eu.pnu.com
authors.forename: R
authors.initials: R
authors.lastname: Movérare
authors.forename: L
authors.initials: L
authors.lastname: Elfman
authors.forename: E
authors.initials: E
authors.lastname: Björnsson
authors.forename: G
authors.initials: G
authors.lastname: Stålenheim
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy; D011058:Pollen / Q000276:immunology / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy*; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014197:Trees / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D015848:Interleukin-5; D013745:Tetanus Toxoid; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma