Abstract：Objective To study the clinical effect and mechanisms of specific sublingual immunotherapy (SLIT) for the treatment of allergic rhinitis or asthma in children. Methods Thirty children suffering from Dermatophagoides farinae-allergic rhinitis or asthma (case group) and 30 healthy children (control group) were enrolled in this study. The case group accepted SLIT between January and December 2011. The ratio of forced expiratory volume in one second (FEV1) and its expected value, the ratio of airway resistance and its expected value, peripheral blood eosinophil (Eos) count and serum levels of IL-17 and IL-35 were measured before treatment and one and two years after treatment. The rhinitis or asthma symptom scores were rated and the level of asthma control was monitored. Results Serum IL-17 level in the case group was significantly higher than in the control group before treatment and one year after treatment (P<0.01). Furthermore, serum IL-17 level in the case group gradually decreased from before treatment to 1 year to 2 years after treatment (P<0.01). By two years of treatment, there was no significant difference in serum IL-17 level between the case and control groups (P>0.05). The changes of serum IL-35 level after treatment were opposite to serum IL-17 in the case group. The ratio of FEV1 and its expected value gradually increased from before treatment to 1 year to 2 years after treatment (P<0.01) in the case group. In contrast, the change of the ratio of airway resistance and its expected value and Eos count gradually decreased from before treatment to 1 year to 2 years after treatment (P<0.01) in the case group. More patients achieved improved rhinitis or asthma symptom scores two years after treatment than one year after treatment in the case group (P<0.01). SLIT was effective in 85% of children with allergic rhinitis one after treatment vs 100% two years after treatment. Asthma control was observed in 76% of the asthmatic patients one after treatment vs 92% two years after treatment. Conclusions SLIT is effective for allergic rhinitis and asthma in children, and the treatment period of two years seems to be superior to one year. The mechanism of action of SLIT for the treatment of allergic rhinitis and asthma may be associated with inhibition of IL-17 expression and promotion of IL-35 expression.
DING Lian-Fu,CHEN Qiang,LI Lan et al. Effects of sublingual immunotherapy on serum IL-17 and IL-35 levels in children with allergic rhinitis or asthma[J]. CJCP, 2014, 16(12): 1206-1210.
MizuTani N, Goshima H, Nabe T, eT al. ComplemenT C3a-induced IL-17 plays a criTical role in an IgE-mediaTed laTe-phase asThmaTic response and airway hyperresponsiveness via neuTrophilic inflammaTion in mice[J]. J Immunol, 2012, 188(11): 5694-5705.
[2]
Naundorf S, Schroder M, Hoflich C, eT al. IL-10 inTerferes direcTly wiTh TCR-induced IFN-gamma buT noT IL-17 producTion in memory T cells[J]. Eur J Immunol, 2009, 39(4): 1066-1077.
[3]
WhiTehead GS, Wilson RH, Nakano K, eT al. IL-35 producTion by inducible cosTimulaTor (ICOS)-posiTive regulaTory T cells reverses esTablished IL-17-dependenT allergic airways disease[J]. J Allergy Clin Immunol, 2012, 129(1): 207-215.
Oboki K, Ohno T, SaiTo H, eT al. Th17 and allergy[J]. Allergol InTern, 2008, 57(2):121-134.
[13]
Ciprandi G, De Amici M, Murdaca G, eT al. Serum inTerleukin-17 levels are relaTed To clinical severiTy in allergic rhiniTis[J]. Allergy, 2009, 64(9): 1375-1378.
[14]
Olson BM, Sullivan JA, Burlingham WJ. InTerleukin 35: a key mediaTor of suppression and The propagaTion of infecTious Tolerance[J]. FronT Immunol, 2013, 4: 315.
[15]
Lee S, Hwang HJ, Kim Y. Modeling The role of TGF-β in regulaTion of The Th17 phenoType in The LPS-driven immune sysTem[J]. Bull MaTh Biol, 2014, 76(5): 1045-1080.
[16]
Collison LW, Workman CJ, Kuo TT, eT al. The inhibiTory cyTokine IL-35 conTribuTes To regulaTory T-cell funcTion[J]. NaTure, 2007, 450(7169): 566-569.
Liu JQ, Liu Z, Zhang X, eT al. Increased Th17 and regulaTory T cell responses in EBV-induced gene 3-deficienT mice lead To marginally enhanced developmenT of auToimmune encephalomyeliTis[J]. J Immunol, 2012, 188(7): 3099-3106.
[19]
KocheTkova I, Golden S, Holderness K, eT al. IL-35 sTimulaTion of CD39+ regulaTory T cells confers proTecTion againsT collagen II-induced arThriTis via The producTion of IL-10[J]. J Immunol, 2010, 184(12): 7144-7153.
[20]
Huang CH, Loo EX, Kuo IC, eT al. Airway inflammaTion and IgE producTion induced by dusT miTe allergen-specific memory/effecTor Th2 cell line can be effecTively aTTenuaTed by IL-35[J]. J Immunol, 2011,187(1): 462-471.
[21]
Incorvaia C, Masieri S, ScuraTi S, eT al. The currenT role of sublingual immunoTherapy in The TreaTmenT of allergic rhiniTis in adulTs and children[J]. J AsThma Allergy, 2011, 4: 13-17.
[22]
Canonica GW, BousqueT J, Casale T, eT al. Sub-lingual immunoTherapy: World Allergy OrganizaTion PosiTion Paper 2009[J]. Allergy, 2009, 64 Suppl 91: 1-59.
