TY - JOUR
T1 - Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance
AU - Kuruma, Tadao
AU - Maruyama, Toru
AU - Hiramatsu, Shin ichi
AU - Yasuda, Yuichiro
AU - Yasuda, Shioto
AU - Odashiro, Keita
AU - Harada, Mine
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Background: Although amiodarone is a potent antiarrhythmic agent, its clinical use is limited by serious lung toxicity. This study investigated the mechanisms of amiodarone-induced lung toxicity from an immunological perspective. Because interferon gamma (IFN-γ: Th1 cytokine) inhibits pulmonary fibroblast proliferation whereas interleukin-4 (IL-4: Th2 cytokine) augments fibroblast growth and collagen production, we hypothesized that amiodarone lung toxicity is related to Th1/Th2 balance. Methods: Twenty-six consecutive Japanese patients with ventricular arrhythmias treated with amiodarone were enrolled in this study and were divided into two groups. Group A contained patients demonstrating amiodarone lung toxicity diagnosed by chest X-ray, KL-6 or DLCO (n = 6), whereas group B included patients treated without any adverse effects (n = 20). Th1/Th2 balance was investigated by the ratio of IFN-γ and IL-4 produced by activated peripheral CD4+ T cells. Results: Clinical baseline characteristics prior to oral amiodarone did not show any differences between group A and group B except for DLCO (82.0 ± 5.2% vs. 90.8 ± 9.0%, p = 0.032) and Th1/Th2 balance (7.98 ± 1.68 vs. 13.34 ± 5.10, p = 0.020). This balance was not altered three months after withdrawal of amiodarone in group A and under continued treatment in group B, suggesting patient-specific rather than amiodarone-induced. After starting amiodarone, serum concentration of desethylamiodarone was greater in group A than in group B (p = 0.009) and was inversely proportional to Th1/Th2 ratio (p = 0.013). Multilogistic regression analysis indicated that Th1/Th2 balance was the most powerful indicator of amiodarone lung toxicity (p = 0.046, odds ratio of 0.424). Conclusions: Although large cohort is required, the present study indicates that Th1/Th2 balance may influence amiodarone metabolism and may be a powerful indicator of amiodarone-induced subclinical lung toxicity at least in Japanese.
AB - Background: Although amiodarone is a potent antiarrhythmic agent, its clinical use is limited by serious lung toxicity. This study investigated the mechanisms of amiodarone-induced lung toxicity from an immunological perspective. Because interferon gamma (IFN-γ: Th1 cytokine) inhibits pulmonary fibroblast proliferation whereas interleukin-4 (IL-4: Th2 cytokine) augments fibroblast growth and collagen production, we hypothesized that amiodarone lung toxicity is related to Th1/Th2 balance. Methods: Twenty-six consecutive Japanese patients with ventricular arrhythmias treated with amiodarone were enrolled in this study and were divided into two groups. Group A contained patients demonstrating amiodarone lung toxicity diagnosed by chest X-ray, KL-6 or DLCO (n = 6), whereas group B included patients treated without any adverse effects (n = 20). Th1/Th2 balance was investigated by the ratio of IFN-γ and IL-4 produced by activated peripheral CD4+ T cells. Results: Clinical baseline characteristics prior to oral amiodarone did not show any differences between group A and group B except for DLCO (82.0 ± 5.2% vs. 90.8 ± 9.0%, p = 0.032) and Th1/Th2 balance (7.98 ± 1.68 vs. 13.34 ± 5.10, p = 0.020). This balance was not altered three months after withdrawal of amiodarone in group A and under continued treatment in group B, suggesting patient-specific rather than amiodarone-induced. After starting amiodarone, serum concentration of desethylamiodarone was greater in group A than in group B (p = 0.009) and was inversely proportional to Th1/Th2 ratio (p = 0.013). Multilogistic regression analysis indicated that Th1/Th2 balance was the most powerful indicator of amiodarone lung toxicity (p = 0.046, odds ratio of 0.424). Conclusions: Although large cohort is required, the present study indicates that Th1/Th2 balance may influence amiodarone metabolism and may be a powerful indicator of amiodarone-induced subclinical lung toxicity at least in Japanese.
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U2 - 10.1016/j.ijcard.2008.02.027
DO - 10.1016/j.ijcard.2008.02.027
M3 - Article
C2 - 18584899
AN - SCOPUS:64849091989
SN - 0167-5273
VL - 134
SP - 224
EP - 230
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 2
ER -