Premium
Genetic influences in the development of Amiodarone‐induced pulmonary fibrosis (AIPF)
Author(s) -
Hartog Matthew,
Herron Bruce,
Lawrence David,
Ding Xinxin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1107.3
Subject(s) - genetic predisposition , immune system , immunology , population , bronchoalveolar lavage , pulmonary fibrosis , fibrosis , inbred strain , phenotype , cd8 , biology , pulmonary toxicity , toxicity , microarray , drug development , medicine , drug , genetics , pharmacology , gene , lung , gene expression , environmental health
Amiodarone (AMI) is a class III antiarrhythmic drug that is known to cause irreversible pulmonary fibrosis within a subset of humans. The mechanism of toxicity is currently unknown but is thought to involve an immune response component. As there is no clear relationship between dose received and time of onset, and in light of known drug susceptibilities due to DNA polymorphisms, we propose that there may be a genetic predisposition to the development of AIPF. In order to model the genetic diversity of the human population a diverse panel of ten inbred mouse strains was selected. Sub‐acute and chronic treatment models were developed to identify genetically dependent responses predictive of AIPF onset. The toxicity phenotypes will be correlated with previously gathered microarray data from the inbred mouse panel to identify genetic factors relevant to the onset and development of AIPF. Divergent responses in multiple markers of pulmonary immune function, such as total cell count recovered, using bronchoalveolar lavage, total number of macrophages and lymphocytes, and CD4/CD8 T cell ratio, have segregated by genetic background and demonstrate a genetic component in response to AMI treatment.