Allergen-induced in vitro expression of IL-18, SLAM and GATA-3 mRNA in PBMC during sublingual immunotherapy.
BACKGROUND
Signalling lymphocytic activation molecule (SLAM) and interleukin (IL)-18 induce interferon (IFN)-gamma production from Th1 cells. The allergen-induced SLAM and IL-18 mRNA expressions are increased during subcutaneous immunotherapy (SCIT), but nothing is known about their role during sublingual immunotherapy (SLIT). Transcription factor GATA-3 is associated with Th2 cells but its role in SCIT and SLIT is yet unexplored. This study was undertaken to analyse the allergen induced in vitro mRNA expression of IL-18, SLAM and GATA-3 in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR) during SLIT.


METHODS
Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with 24,000 SQ-U of mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included. Peripheral blood mononuclear cell were stimulated with birch extract prior to, after 1 and 2 years of the treatment. The mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan); Applied Biosystems, Foster City, CA, USA).


RESULTS
The expression of IL-18 mRNA was increased in the high-dose group in comparison to the placebo group after 1 year of therapy (P = 0.028) and had an inverse correlation with the late phase skin reaction after the second study year (r = -0.41, P = 0.041). SLAM mRNA expression increased in the high-dose group from baseline to 1 year (P = 0.028) and correlated with IL-10 (r = 0.96, P < 0.0001) and transforming growth factor-beta (r = 0.80, P = 0.0037) mRNA expression. No significant changes were seen in GATA-3 mRNA expression.


CONCLUSIONS
During SLIT, IL-18 and SLAM are upregulated, suggesting that the Th2 type inflammatory response is downregulated during SLIT by increased Th1 type response.
Savolainen
J
J
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.
Nieminen
K
K
Laaksonen
K
K
Laiho
T
T
Jacobsen
L
L
Lahesmaa
R
R
Terho
E O
EO
Valovirta
E
E
D000286:Administration, Sublingual; D000293:Adolescent; D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D029661:Alnus / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D029662:Betula / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D031211:Corylus / Q000235:genetics / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D011058:Pollen / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D000485:Allergens; D015703:Antigens, CD; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020382:Interleukin-18; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1