title: High-altitude climate therapy reduces local airway inflammation and modulates lymphocyte activation.
abstract: High-altitude climate therapy is a well-established therapeutic option, which improves clinical symptoms in asthma. However, little is known about the underlying immunological mechanisms. The study investigates the influence of high-altitude climate therapy on airway inflammation and cellular components of specific and unspecific immune response. Exhaled NO significantly decreased within 3 weeks of therapy in patients with allergic and intrinsic, moderate and severe asthma. Interleukin-10 (IL-10)-secreting peripheral blood mononuclear cells (PBMC) increased within 3 weeks of therapy in six of 11 patients, whereas transforming growth factor-beta(1)-secreting PBMC remained stable. Furthermore, monocyte activation, assessed by CD80 expression significantly decreased during therapy. The frequency of CRTH2-expressing T cells decreased, while regulatory T cells (T(reg)) remained stable. FOXP3 and GATA-3 mRNA expression in CD4(+) T cells did not change, while interferon-gamma and IL-13 mRNA expression decreased in eight of 10 patients. The current data demonstrate that high-altitude climate therapy reduces local airway inflammation. Furthermore, monocytes switch towards a tolerogenic phenotype under high-altitude climate therapy. The T(reg)/Th2 ratio increases; however, because of the absence of antigens/allergens, no de novo differentiation of Th2 nor T(reg) cells is observed. The high-altitude climate therapy therefore may form the immunological basis for the endogenous control of allergen-driven diseases.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, SIAF, Davos Platz, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Karagiannidis
authors.forename: G
authors.initials: G
authors.lastname: Hense
authors.forename: B
authors.initials: B
authors.lastname: Rueckert
authors.forename: P Y
authors.initials: PY
authors.lastname: Mantel
authors.forename: B
authors.initials: B
authors.lastname: Ichters
authors.forename: K
authors.initials: K
authors.lastname: Blaser
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: C B
authors.initials: CB
authors.lastname: Schmidt-Weber
mesh_terms: D000328:Adult; D000531:Altitude; D000938:Antigen-Presenting Cells; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D001991:Bronchitis / Q000628:therapy; D002980:Climate; D050990:GATA3 Transcription Factor; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D019041:L-Selectin / Q000097:blood; D008213:Lymphocyte Activation; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D011971:Receptors, Immunologic / Q000097:blood; D011982:Receptors, Prostaglandin / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014157:Transcription Factors / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018793:Interleukin-13; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D019041:L-Selectin; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; C036293:prostaglandin D2 receptor