Pène J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus C F, Yssel H, Bousquet J
INSERM U. 454, Hôpital Arnaud de Villeneuve, Montpellier, France.
J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):571-8. doi: 10.1016/s0091-6749(98)70294-5.
Cells producing a T(H2)-cytokine profile play an important role in the onset and maintenance of atopic diseases, and therefore specific immunotherapy is aimed to induce a switch to cells producing a T(H1)- or T(H0)-cytokine profile. Recently, a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed, but its mechanisms of action are unknown.
We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests (PD20FEV1) with a standardized Fel d 1 cat extract on Fel d 1-specific serum IgE and IgG levels and in vitro IL-4 and IFN-gamma production.
Patients allergic to cats received 6 weekly injections of 7.5 micro(g) (low dose), 75 micro(g) (medium dose), or 750 micro(g) (high dose) of Fel d 1 peptides (25 patients) or a placebo (6 patients).
Six weeks after ending immunotherapy, posttreatment PD20FEV1 was not significantly different between the treated and placebo groups. However, in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days. IL-4 release was significantly reduced in the high dose-treated group (P <.005, Wilcoxon W test), whereas it was unchanged in the low or medium dose- and in the placebo-treated groups. In all groups, IFN-gamma, IgE, and IgG levels remained unchanged.
There was no correlation between the improvement of PD20FEV1 and the decrease in IL-4 production. These data suggest that peptide immunotherapy may act by shifting the Fel d 1-induced response of PBMCs in vitro from the T(H2)-like to the T(H0)-like phenotype.
产生TH2细胞因子谱的细胞在特应性疾病的发生和维持中起重要作用,因此特异性免疫疗法旨在诱导向产生TH1或TH0细胞因子谱的细胞转变。最近,一种利用主要猫过敏原Fel d 1的合成肽的新型免疫疗法已被开发出来,但其作用机制尚不清楚。
我们研究了用Fel d 1肽进行免疫疗法对用标准化Fel d 1猫提取物进行支气管激发试验(PD20FEV1)的反应、Fel d 1特异性血清IgE和IgG水平以及体外IL-4和IFN-γ产生的影响。
对猫过敏的患者每周接受6次注射,分别注射7.5微克(低剂量)、75微克(中剂量)或750微克(高剂量)的Fel d 1肽(25例患者)或安慰剂(6例患者)。
免疫疗法结束6周后,治疗组和安慰剂组治疗后的PD20FEV1无显著差异。然而,在中剂量和高剂量组中,基线和治疗后天数之间有显著改善。高剂量治疗组的IL-4释放显著降低(P<.005,Wilcoxon W检验),而低剂量或中剂量组以及安慰剂治疗组则无变化。在所有组中,IFN-γ、IgE和IgG水平均保持不变。
PD20FEV1的改善与IL-4产生的减少之间没有相关性。这些数据表明,肽免疫疗法可能通过将体外Fel d 1诱导的PBMC反应从TH2样表型转变为TH0样表型而起作用。