Gogishvili Tea, Hahn Christian, Meinhard Julia, Hohaus Andreas, Erb Klaus, Sebald Walter, Bröcker Eva B, Grunewald Susanne M
Department of Dermatology, University of Wurzburg, Wurzburg, Germany.
Int Arch Allergy Immunol. 2007;142(2):165-74. doi: 10.1159/000096610. Epub 2006 Oct 27.
Successful allergen-specific immunotherapy (SIT) is associated with reduced Th2 cytokine production and the induction of IL-10-producing regulatory T cells. To improve treatment efficacy, we investigated the impact of an IL-4/IL-13 inhibitor during SIT.
BALB/c mice were sensitized intranasally with ovalbumin (OVA) for 4 weeks. Subsequently, they were subjected to intranasal SIT, with OVA being administered at doses increasing from 1 mug to 1 mg over 3 weeks with or without an IL-4/IL-13 inhibitor. Serum OVA-specific antibodies were measured and bronchoalveolar lavage (BAL) fluids were checked for airway eosinophilia. Subsequently, lung tissue was examined histologically for inflammatory infiltrates. Cytokines were detected in BAL fluids and spleen cell cultures. Furthermore, CD4 CD25 double-positive spleen T cells were checked for intracellular IL-10 production by flow cytometry.
OVA sensitization resulted in persistent IgE synthesis and an eosinophil-rich allergic airway inflammation combined with increased IL-4 and IL-5 levels. Therefore, intranasal SIT could efficiently reverse the allergic phenotype. This was associated with decreased IL-4 and IL-5 levels, and increased IL-10 levels in BAL fluids as well as increased amounts of IL-10-producing CD25+ regulatory T cells. However, mice treated with the IL-4/IL-13 inhibitor during SIT did not produce significantly different results .
The use of an IL-4/IL-13 inhibitor as an adjuvant for SIT did not enhance anti-allergic effects. Thus, the observed reversal of Th2 responses during SIT may not be the keystone for successful therapy, but rather other factors, e.g. IL-10-producing regulatory T cells, may be crucial.
成功的变应原特异性免疫疗法（SIT）与Th2细胞因子产生减少以及产生白细胞介素-10（IL-10）的调节性T细胞的诱导有关。为提高治疗效果，我们研究了一种IL-4/IL-13抑制剂在SIT期间的作用。
用卵清蛋白（OVA）经鼻致敏BALB/c小鼠4周。随后，对其进行经鼻SIT，在3周内给予OVA，剂量从1微克增加到1毫克，同时给予或不给予IL-4/IL-13抑制剂。检测血清OVA特异性抗体，并检查支气管肺泡灌洗（BAL）液中的气道嗜酸性粒细胞增多情况。随后，对肺组织进行组织学检查以观察炎症浸润。在BAL液和脾细胞培养物中检测细胞因子。此外，通过流式细胞术检查CD4 CD25双阳性脾T细胞的细胞内IL-10产生情况。
OVA致敏导致持续的IgE合成以及富含嗜酸性粒细胞的过敏性气道炎症，并伴有IL-4和IL-5水平升高。因此，经鼻SIT可有效逆转过敏表型。这与BAL液中IL-4和IL-5水平降低、IL-10水平升高以及产生IL-10的CD25+调节性T细胞数量增加有关。然而，在SIT期间用IL-4/IL-13抑制剂治疗的小鼠未产生显著不同的结果。
使用IL-4/IL-13抑制剂作为SIT的佐剂并未增强抗过敏作用。因此，在SIT期间观察到的Th2反应逆转可能不是成功治疗的关键因素，而其他因素，例如产生IL-10的调节性T细胞，可能至关重要。
