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. 2004 Mar;59(3):224–230. doi: 10.1136/thx.2003.010785

Retinoic acid fails to reverse emphysema in adult mouse models

M Fujita 1, Q Ye 1, H Ouchi 1, N Nakashima 1, N Hamada 1, N Hagimoto 1, K Kuwano 1, R Mason 1, Y Nakanishi 1
PMCID: PMC1746974  PMID: 14985558

Abstract

Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α 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-α 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-α 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.

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Selected References

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