TUMOR-NECROSIS-FACTOR-ALPHA INCREASES AIRWAY RESPONSIVENESS AND SPUTUM NEUTROPHILIA IN NORMAL HUMAN-SUBJECTS

被引:297
作者
THOMAS, PS [1 ]
YATES, DH [1 ]
BARNES, PJ [1 ]
机构
[1] NATL HEART & LUNG INST,DEPT THORAC MED,LONDON,ENGLAND
关键词
D O I
10.1164/ajrccm.152.1.7599866
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
The effect of inhaled recom binant human tumor necrosis factor-alpha (rhTNF alpha) on airway responsiveness and the cellular composition of sputum was studied in eight normal subjects using a placebo-controlled study design. Spirometric data and bronchial responsiveness (BR) to methacholine were studied, and an estimate of pulmonary-cell infiltration was made using the technique of induced sputum. A single dose of mTN Fa (60 ng) caused an increase in BR, with a leftward shift in the concentration-based response to methacholine at all time points after inhalation, as compared with a saline control challenge. Likewise, there was a decrease in the log provocative concentration of methacholine causing a 15% decrease in FEV(1), which reached a maximum at 24 h (1.37 +/- 0.22 versus 1.87 +/- 0.24, rhTNF alpha and control, respectively; p < 0.05). No change was observed in baseline spirometric measures at any of the time points. A significant increase in the percentage of neutrophils occurred in the induced sputum, reaching a maximum at 24 h (44.2 +/- 9.9% versus 16.6 +/- 7.1%, rhTNF alpha and control, respectively; p < 0.05). We conclude that TNF alpha can induce an increase in airway responsiveness in normal subjects, and is associated with a neutrophil infiltration, thus making it a candidate cytokine for the induction of airway inflammation and hyperresponsiveness.
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页码:76 / 80
页数:5
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