Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects

Am J Respir Crit Care Med. 1995 Jul;152(1):76-80. doi: 10.1164/ajrccm.152.1.7599866.


The effect of inhaled recombinant 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 rhTNF alpha (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 FEV1, 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aerosols
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Cell Count
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Methacholine Chloride
  • Neutrophils / cytology*
  • Recombinant Proteins / pharmacology
  • Spirometry
  • Sputum / cytology*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Aerosols
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Methacholine Chloride