American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 1605b-1606, (2005)
© 2005 American Thoracic Society
From the Authors:
We are grateful for the interest in our recently published article (1) by Drs. Cottin and Cordier, who suggest that the mouse strain we used (SP-C/TNF- ) might be a model of combined pulmonary fibrosis and emphysema (CPFE). We are aware of the syndrome (2, 3) and alluded to the coexistence of fibrosis and emphysema in the discussion of our paper.
While our current mouse model may capture some features displayed in CPFE, we are, however, not convinced that it represents the clinical syndrome itself. We observed widespread consolidation of the lung tissue with significant fibrosis concomitant with loss of small airspaces. In fact, the surprise was the lack of large airspace formation, which characterizes emphysema, despite an increase of lung volume and decreased elastance.
There are other inflammatory mediators such as MMP-12 that have been shown to produce a pathogenesis of pulmonary fibrosis and chronic obstructive pulmonary disease in mice (4). It has also been shown that a reduction of vascular endothelial growth factor (VEGF) may lead to emphysema in mice (5). Furthermore, VEGF was also decreased in idiopathic pulmonary fibrosis and pulmonary fibrosis associated with connective tissue disease in humans (6). In yet another report, overexpression of interleukin-1 was shown to cause lung inflammation, airway fibrosis and distal airspace enlargement (7). Thus, it is clear that similar phenotypes can be achieved with several mediators and presumably different pathways. We believe that although TNF- is a pivotal pathologic mediator, its ubiquity in different diseases makes it less likely to be the single cause of any one disease or syndrome. That is not to say that somewhere along the mediator cascade there might be a culpable mediator, but that has yet to be shown both in emphysema and in fibrotic diseases.
Lennart K. A. Lundblad,
John Thompson-Figueroa,
Timothy Leclair,
Michael J. Sullivan,
Matthew E. Poynter,
Charles G. Irvin and
Jason H. T. Bates
The University of Vermont Vermont Lung Center Burlington, Vermont
FOOTNOTES
Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
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Copyright © 2005 American Thoracic Society
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