Walden S M, Proud D, Bascom R, Lichtenstein L M, Kagey-Sobotka A, Adkinson N F, Naclerio R M
Department of Medicine, Johns Hopkins University, Baltimore, MD.
J Allergy Clin Immunol. 1988 May;81(5 Pt 2):940-9. doi: 10.1016/0091-6749(88)90157-1.
To investigate the pathogenesis of allergic rhinitis, we developed a nasal challenge model in which we examined the early, late, and rechallenge responses to antigen provocation. In these three aspects of the allergic reaction the physiologic responses are associated with inflammatory mediator release. Whereas the early response appears to be related mainly to mast cell activation and mediator release, the late reaction involves a different pattern of mediator release and an inflammatory cell influx, consisting of basophils, neutrophils, and eosinophils. Rechallenge with antigen 11 hours later results in an augmented immediate response. Pretreatment with aspirin reduces the levels of cyclooxygenase metabolites in nasal secretions without affecting the immediate physiologic response to antigen or the expected increase in the levels of histamine, N-alpha-tosyl-L-arginine methyl ester-esterase activity, and leukotriene C4. Pretreatment with systemic steroids does not affect the early allergic response, but significantly reduces mediator release during the late and rechallenge responses. The influx of eosinophils is inhibited by pretreatment with systemic steroids, but neutrophil influx is not. In contrast, pretreatment with topical steroids blocks the early response and the late and rechallenge responses. Influx of all cell types, including the neutrophil, was prevented. These studies show unequivocally that an inflammatory process follows the initial response to antigen and that this inflammation is affected by drugs important in the treatment of chronic allergic disease. We speculate that understanding allergic inflammation will lead to new therapeutic development.
为了研究变应性鼻炎的发病机制，我们建立了一种鼻激发模型，在此模型中我们检测了对抗原激发的早期、晚期和再次激发反应。在变态反应的这三个方面，生理反应与炎症介质的释放相关。早期反应似乎主要与肥大细胞活化和介质释放有关，而晚期反应涉及不同模式的介质释放和炎症细胞浸润，包括嗜碱性粒细胞、中性粒细胞和嗜酸性粒细胞。11小时后用抗原再次激发会导致即刻反应增强。阿司匹林预处理可降低鼻分泌物中环氧化酶代谢产物的水平，而不影响对抗原的即刻生理反应或组胺、N-α-对甲苯磺酰-L-精氨酸甲酯酯酶活性和白三烯C4水平的预期升高。全身用类固醇预处理不影响早期变态反应，但可显著降低晚期和再次激发反应期间的介质释放。全身用类固醇预处理可抑制嗜酸性粒细胞浸润，但不能抑制中性粒细胞浸润。相比之下，局部用类固醇预处理可阻断早期反应以及晚期和再次激发反应。包括中性粒细胞在内的所有细胞类型的浸润均被阻止。这些研究明确表明，在对抗原的初始反应之后会发生炎症过程，并且这种炎症受到在慢性变应性疾病治疗中重要的药物的影响。我们推测，了解变应性炎症将带来新的治疗进展。
