title: Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios.
abstract: Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.
authors.affiliation: Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Wachholz
authors.forename: Kayhan T
authors.initials: KT
authors.lastname: Nouri-Aria
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Wilson
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Walker
authors.forename: Adrienne
authors.initials: A
authors.lastname: Verhoef
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Till
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D007371:Interferon-gamma