Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC.
BACKGROUND
During subcutaneous immunotherapy (SCIT), there is a local mucosal shift from Th2 to Th1 type cytokine predominance and downregulation of interleukin (IL)-5 and eosinophilia. According to recent studies IL-10- and transforming growth factor (TGF)-beta-induced tolerance is another key phenomenon in SCIT. Few data to date is available on mechanisms and roles of these cytokines in sublingual immunotherapy (SLIT).


METHODS
This study was undertaken to analyse the allergen-induced in vitro mRNA expression of IL-4, IL-5, IL-10, TGF-beta and interferon (IFN)-gamma during SLIT in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR).


METHODS
Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with a weekly dose of 24,000 SQ-U of glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included in the study. Peripheral blood mononuclear cell samples were collected and stimulated with pollen allergen extract prior to the treatment, after 1 and 2 years of the treatment. The cytokine mRNA expression was assessed using kinetic real time reverse transcription polymerase chain reaction (RT-PCR; TaqMan).


RESULTS
The in vitro allergen-induced mRNA expression of IL-5 by PBMC in the placebo group at 1 (P = 0.0065) and 2 (P = 0.013) years of therapy were increased in comparison with the highest dose. The expression of IL-10 mRNA was increased in the highest dose group (P = 0.0016) and the lower dose group (P = 0.034) at 2 years of therapy when compared with placebo. The change in the expression of allergen-induced TGF-beta had an inversed correlation with the change of IL-5 (r = -0.38, P = 0.036) and positive correlation with the change of IL-10 (r = 0.58, P = 0.0019).


CONCLUSIONS
Sublingual immunotherapy induced a dose-dependent systemic allergen-specific immunological response in children with AR. During high-dose SLIT, there was activation of regulatory cytokine IL-10 and an inhibitory effect on IL-5 expression increase that was associated with TGF-beta.
Savolainen
J
J
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.
Jacobsen
L
L
Valovirta
E
E
D000286:Administration, Sublingual; D000293:Adolescent; D000485:Allergens / Q000494:pharmacology; D029661:Alnus / Q000009:adverse effects / Q000276:immunology; D029662:Betula / Q000009:adverse effects / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D031211:Corylus / Q000009:adverse effects / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma