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.
引用
收藏
页码:76 / 80
页数:5
相关论文
共 35 条
[21]  
Klebanoff S.J., Vadas M.A., Harlan J.M., Sparks L.H., Gamble J.R., Agosti J.M., Waltersdorph A.M., Stimulation of neutrophils by tumor necrosis factor, J. Immunol., 136, pp. 4220-4225, (1986)
[22]  
Ming W.J., Bersani L., Mantovani A., Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leucocytes, J. Immunol., 87, pp. 1469-1474, (1987)
[23]  
Nagy L., Lee T.H., Kay A.B., Neutrophil chemotactic activity in antigen-induced late asthmatic reactions, N. Engl. J. Med., pp. 497-501, (1982)
[24]  
Diaz P., Gonzales C., Galleguillos F., Anic P., Kay A.B., Eosinophils and macrophages in bronchial mucus and bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions, J. Allergy Clin. Immunol., 77, pp. 244-249, (1986)
[25]  
Metzger W.J., Richerson H.B., Worden K., Monick M., Hunninghake G.W., Bronchoalveolar lavage of allergic asthmatic patients following allergen bronchoprovocation, Chest, 89, pp. 477-483, (1986)
[26]  
Gratziou C., Carroll M., Montefort S.T., Walls A., Howarth P., Holgate S.T., Inflammatory cellular events in BAL of asthmatic airways 6 hours after endobronchial allergen challenge, Am. Rev. Respir. Dis., 147, (1993)
[27]  
Hakanssonn L., Carlson M., Stalenheim G., Venge P., Migratory responses of eosinophil and neutrophil granulocytes from patients with asthma, J. Allergy Clin. Immunol., 85, pp. 743-750, (1990)
[28]  
Meltzer S., Goldberg B., Lad P., Easton J., Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma, J. Allergy Clin. Immunol., 83, pp. 960-966, (1989)
[29]  
Hallahan A.R., Armour C.L., Black J.L., Products of neutrophils and eosinophils increase the responsiveness of human isolated bronchial tissue, Eur. Respir. J., 3, pp. 554-558, (1990)
[30]  
Ulich T.R., Watson L.R., Yin S., Guo K.Z., Wang P., Thang H., Castillo J., The intra-tracheal administration of endotoxin and cytokines, Am. J. Pathol., 138, pp. 1485-1496, (1991)