Hamilos D L, Thawley S E, Kramper M A, Kamil A, Hamid Q A
Department of Medicine , Washington University School of Medicine, St Louis, MO 63110, USA.
J Allergy Clin Immunol. 1999 Jan;103(1 Pt 1):79-87. doi: 10.1016/s0091-6749(99)70529-4.
Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone.
We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1beta).
Twenty subjects (9 women and 11 men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of 1 month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 microg or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test.
Fluticasone treatment significantly reduced NP eosinophilia (P =.02) and CD4(+) T lymphocytes (P =.02). Eosinophils expressing the marker EG2 were more significantly reduced (P =.007). Fluticasone also reduced the expression of P-selectin (P =.005) and the number of IL-4 and IL-13 mRNA+ cells (P =.02 and.05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1beta mRNA+ cells in the polyps.
We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment.
鼻息肉（NP）疾病对鼻内用类固醇治疗呈现出逐渐的反应。我们推测促进NP嗜酸性粒细胞增多的各种炎症特征对鼻内用氟替卡松治疗会表现出不同的敏感性。
我们进行了一项为期4周的双盲、安慰剂对照试验，使用丙酸氟替卡松鼻内给药或匹配的安慰剂，以评估它们在减少NP炎症细胞、内皮血管细胞黏附分子（VCAM）-1和P-选择素的表达以及参与诱导一组黏附分子的细胞因子（即IL-4、IL-13、TNF-α和IL-1β）表达方面的有效性。
研究了20名患有严重慢性鼻窦炎和NP的受试者（9名女性和11名男性）。在研究前，全身用和鼻内用类固醇分别停用至少1个月和2周。在每侧鼻孔每日两次给予100微克鼻内用氟替卡松或安慰剂治疗前1周和治疗后4周获取NP的活检标本。活检标本速冻用于免疫染色或固定在多聚甲醛中用于原位杂交。用Wilcoxon符号秩检验分析治疗前至治疗后的结果。
氟替卡松治疗显著降低了NP嗜酸性粒细胞增多（P = 0.02）和CD4(+) T淋巴细胞（P = 0.02）。表达标志物EG2的嗜酸性粒细胞减少更为显著（P = 0.007）。氟替卡松还降低了P-选择素的表达（P = 0.005）以及IL-4和IL-13 mRNA+细胞的数量（分别为P = 0.02和0.05）。相比之下，氟替卡松并未显著降低息肉中内皮VCAM-1的表达或TNF-α或IL-1β mRNA+细胞的数量。
我们得出结论，鼻内用氟替卡松减少了NP炎症，但促炎细胞因子的表达和内皮VCAM-1相对不受氟替卡松治疗的影响。尽管进行了鼻内用类固醇治疗，这些后期的炎症特征可能导致NP疾病持续存在。
