The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma

Retrovirology

Ali Bazarbachi⁸  Mahmoud Mahmoudi^1,10  Olivier Hermine²  Hugues de Thé³  Ardeshir Ghavamzadeh⁷  Hossein Rahimi⁶  Mohamad Ezzedine¹  Zeina Dassouki⁸  Abbas Shirdel⁶  Roudaina Nasser⁸  Mohamad Mortada¹  Fadwa Berry¹  Hiba El Hajj⁸  Mohamad-Mehdi Kooshyar⁶  Mahdi Tarhini⁹  Houshang Rafatpanah^1,10  Akram Ghantous⁴  Reza Farid^1,10  SA Rahim Rezaee⁵  Ghada Kchour¹ 

[1] Department of Biology, Faculty of Sciences, Lebanese University, Hadath, Lebanon;CNRS UMR 8147, Hôpital Necker, Paris, France;INSERM UMR 944 and CNRS UMR 7212, Hôpital Saint Louis, Paris, France;Lebanese American University, School of Arts and Sciences, Beirut, Lebanon;Microbiology and Virology Research Center, Bu-Ali Research institute, Mashhad University of Medical Sciences, Mashhad, Iran;Department of Internal Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Tehran University of Medical Sciences, Tehran, Iran;Department of Internal Medicine, American University of Beirut, Beirut, Lebanon;Faculty of Nursing Sciences, Islamic University, Beirut, Lebanon;Immunology Research Centre Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

关键词: Immune deficiency;    Cytokines;    ATL;    HTLV-I;    Zidovudine;    Interferon;    Arsenic;   

Others  :  1209069
DOI  :  10.1186/1742-4690-10-91

 received in 2013-04-25, accepted in 2013-07-22,  发布年份 2013

【 摘 要 】

Background

HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN.

Results

Here we assessed Th1/Th2/T_reg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T_reg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4⁺CD25⁺ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4⁺CD25⁺ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30.

Conclusions

The observed shift from a T_reg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

【 授权许可】

   
2013 Kchour et al.; licensee BioMed Central Ltd.

【 图 表 】

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