Increased expression of allergen-induced in vitro interleukin-10 and interleukin-18 mRNA in peripheral blood mononuclear cells of allergic rhinitis patients after specific immunotherapy.
BACKGROUND
During specific pollen immunotherapy (SIT) there is a local mucosal shift from Th2- to Th1- type cytokine predominance, with IL-12 having a major role in this shift. IL-10-induced tolerance is supposed to be a key phenomenon in venom immunotherapy (VIT). However, the role of Th1-promoting cytokines, on the one hand, and the role of regulatory cytokines, on the other hand, have not been studied in parallel during SIT.


OBJECTIVE
This study was undertaken to analyse the allergen-induced in vitro mRNA expression of Th1-type effector cytokine IL-18 and regulatory cytokines IL-10 and TGF-beta during SIT in peripheral blood mononuclear cells (PBMC) of allergic rhinitis (AR) patients.


METHODS
Thirty patients with AR undergoing pollen SIT and 10 patients with AR who were not treated with SIT were included in the study. The symptoms and medications were registered post-seasonally before the beginning of SIT and after 1 year of therapy. PBMC samples were collected and stimulated with pollen allergen extract prior to the treatment, at the maintenance phase in 12 patients and after 1 year of the treatment. The cytokine mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan).


RESULTS
There was a clear increase in the treated AR patients, in comparison with untreated AR patients, in the expression of both IL-10 (mean change from baseline (SEM): 3.1 (0.8) vs. -0.3 (0.3), P<0.002, Mann-Whitney U-test) and IL-18 (2.7 (0.9) vs. -0.2 (0.6), P<0.03) mRNA after 1 year. The clearest increase in IL-10 mRNA expression was seen in patients who did not benefit at all (6.0 (2.3), P<0.001 vs. untreated) and the least increase in patients that had the greatest reduction of symptoms (0.8 (0.6), n.s. vs. untreated) at 1 year. The clearest increase in IL-18 mRNA expression was seen in patients with moderate outcome (3.4 (1.6), P<0.04 vs. untreated). In intermediate samples, taken when the maintenance dose was reached, the peak expression of allergen-induced IL-10 mRNA was associated with the most favourable outcome of SIT (P=0.01, Fisher exact test). A similar trend was seen in IL-18 mRNA expression.


CONCLUSIONS
The results suggest that an early and transient increase in allergen-specific IL-10 and IL-18 mRNA expression in PBMC is essential for the therapeutic outcome after 1 year of SIT.
Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland. johannes.Savolainen@utu.fi
J
J
Savolainen
K
K
Laaksonen
A
A
Rantio-Lehtimäki
E O
EO
Terho
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000494:pharmacology; D002478:Cells, Cultured; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D011058:Pollen; D012333:RNA, Messenger / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors
D000485:Allergens; D020382:Interleukin-18; D012333:RNA, Messenger; D016753:Interleukin-10