AIRWAY BIOLOGY

Retinoic acid fails to reverse emphysema in adult mouse models

M Fujita¹, Q Ye¹, H Ouchi¹, N Nakashima¹, N Hamada¹, N Hagimoto¹, K Kuwano¹, R J Mason², Y Nakanishi¹

¹ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA

Correspondence to:
Correspondence to:
M Fujita MD
Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashiku, Fukuoka 812-8582, Japan; fujita{at}kokyu.med.kyushu-u.ac.jp

Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid.

Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)- transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses.

Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF- transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF- transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model.

Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.

Keywords: emphysema; retinoic acid; tumour necrosis factor ; keratinocyte chemoattractant

Abbreviations: Cstat, static expiratory compliance; FRC, functional residual capacity; KC, keratinocyte chemoattractant; TLC, total lung capacity; TNF-, tumour necrosis factor

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