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(Chest. 2003;124:2283-2292.)
© 2003 American College of Chest Physicians

High Expression of p40tax and Pro-inflammatory Cytokines and Chemokines in the Lungs of Human T-Lymphotropic Virus Type 1-Related Bronchopulmonary Disorders*

Yoriko Yamazato, MD; Akiko Miyazato, MD; Kazuyoshi Kawakami, MD; Satomi Yara, MD; Hiroshi Kaneshima, MD and Atsushi Saito, MD

* From the First Department of Internal Medicine (Drs. Yamazato, Miyazato, Kawakami, Yara, and Saito), Faculty of Medicine, University of the Ryukyus; and Urasoe General Hospital (Dr. Kaneshima), Okinawa, Japan.

Correspondence to: Kazuyoshi Kawakami, MD, PhD, The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan; e-mail: kawakami{at}med.u-ryukyu.ac.jp

Study objective: Human T-lymphotropic virus type 1 (HTLV-1) is closely associated with the development of certain pulmonary diseases, such as bronchiolitis, although the pathologic mechanism remains unclear. To elucidate the pathogenesis of HTLV-1–associated bronchopulmonary disorders, we analyzed the relationship between expression of p40tax, a regulatory component of HTLV-1 that stimulates various host genes, and synthesis of pro-inflammatory cytokines and chemokines by cells in BAL fluid (BALF) obtained from HTLV-1–infected patients.

Design: Reverse transcription-polymerase chain reaction was used to compare the expression of p40tax and pro-inflammatory cytokines and chemokines messenger RNA (mRNA) in BALF of 10 HTLV-1 carriers and 7 healthy subjects. We also studied the correlation between these parameters and the proportion of lymphocytes in BALF.

Results: The expression levels of pro-inflammatory cytokines (interferon [IFN]-{gamma}, interleukin-2) and chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1{alpha}, IFN-{gamma}–inducible protein-10 [IP-10]) were significantly higher in BALF of patients than of healthy subjects. The expression of IFN-{gamma} and MIP-1{alpha} mRNA correlated with that of p40tax. IFN-{gamma} and IP-10 mRNA expression correlated with the proportion of lymphocytes in BALF. The percentage of lymphocytes in BALF increased with higher expression levels of p40tax mRNA, although the correlation was not significant.

Conclusion: Our results suggested that p40tax seems be involved in the development of HTLV-1–associated bronchopulmonary disorders at least in part through the local production of pro-inflammatory cytokines and chemokines.

Key Words: human T-lymphotropic virus type 1 • lung disease • p40tax • pro-inflammatory cytokines, chemokines






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