Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance

Tadao Kuruma, Toru Maruyama, Shin ichi Hiramatsu, Yuichiro Yasuda, Shioto Yasuda, Keita Odashiro, Mine Harada

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)224-230
Number of pages7
JournalInternational Journal of Cardiology
Volume134
Issue number2
DOIs
Publication statusPublished - May 15 2009

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Th1-Th2 Balance
Amiodarone
Lung
Interleukin-4
Fibroblasts
Cytokines
Interferon-gamma

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance. / Kuruma, Tadao; Maruyama, Toru; Hiramatsu, Shin ichi; Yasuda, Yuichiro; Yasuda, Shioto; Odashiro, Keita; Harada, Mine.

In: International Journal of Cardiology, Vol. 134, No. 2, 15.05.2009, p. 224-230.

Research output: Contribution to journalArticle

Kuruma, Tadao ; Maruyama, Toru ; Hiramatsu, Shin ichi ; Yasuda, Yuichiro ; Yasuda, Shioto ; Odashiro, Keita ; Harada, Mine. / Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance. In: International Journal of Cardiology. 2009 ; Vol. 134, No. 2. pp. 224-230.
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abstract = "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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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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