Masuyama K, Jacobson M R, Rak S, Meng Q, Sudderick R M, Kay A B, Lowhagen O, Hamid Q, Durham S R
Department of Allergy & Clinical Immunology, National Heart & Lung Institute, London, U.K.
Immunology. 1994 Jun;82(2):192-9.
Allergen-induced late nasal responses are associated with recruitment and activation of T lymphocytes and eosinophils and preferential mRNA expression for T-helper type 2 (Th2) cytokines. We tested the hypothesis that topical corticosteroids may inhibit late responses by inhibiting cells expressing mRNA for Th2 cytokines. A randomized double-blind placebo-controlled trial of topical corticosteroid (fluticasone propionate) was performed in 48 adult grass pollen-sensitive patients. Nasal biopsies were taken at baseline and repeated 24 hr after local nasal allergen provocation following 6 weeks treatment with either fluticasone propionate 200 micrograms or placebo nasal spray twice daily. Baseline mRNA expression for interleukin-4 (IL-4) (P = 0.01) and IL-5 (P = 0.002) was higher in the patients than in normal controls. Topical corticosteroid treatment significantly inhibited immediate nasal symptoms, with almost complete inhibition of the late response following allergen challenge. This was associated with a marked decrease in the allergen-induced increases in cells expressing mRNA for IL-4 (P = 0.002) but not for IL-5. Inhibition of the late response was also accompanied by decreases in CD25+ cells, presumed T lymphocytes and eosinophils. A significant correlation was observed between the decreases in IL-4 mRNA+ cells and in eosinophils after treatment (r = 0.46, P < 0.05). These results suggest that prolonged treatment with topical corticosteroid inhibits allergen-induced early and late nasal responses and the associated tissue eosinophilia, and that, at least in part, this may result from inhibition of cells expressing mRNA for IL-4.
变应原诱导的迟发性鼻反应与T淋巴细胞和嗜酸性粒细胞的募集及活化相关,且2型辅助性T细胞(Th2)细胞因子的mRNA表达具有偏好性。我们检验了这样一个假说,即局部用皮质类固醇可能通过抑制表达Th2细胞因子mRNA的细胞来抑制迟发性反应。对48名成年草花粉敏感患者进行了一项局部用皮质类固醇(丙酸氟替卡松)的随机双盲安慰剂对照试验。在基线时进行鼻活检,并在每天两次使用200微克丙酸氟替卡松或安慰剂鼻喷雾剂治疗6周后,于局部鼻变应原激发后24小时重复进行活检。患者白细胞介素-4(IL-4)(P = 0.01)和IL-5(P = 0.002)的基线mRNA表达高于正常对照。局部用皮质类固醇治疗显著抑制了即刻鼻症状,变应原激发后的迟发性反应几乎完全被抑制。这与变应原诱导的表达IL-4 mRNA的细胞增加显著减少相关(P = 0.002),但与IL-5无关。迟发性反应的抑制还伴随着假定的T淋巴细胞和嗜酸性粒细胞的CD25 +细胞减少。治疗后IL-4 mRNA +细胞减少与嗜酸性粒细胞减少之间观察到显著相关性(r = 0.46,P < 0.05)。这些结果表明,局部用皮质类固醇的长期治疗可抑制变应原诱导的早期和迟发性鼻反应以及相关的组织嗜酸性粒细胞增多,并且至少部分原因可能是抑制了表达IL-4 mRNA的细胞。