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

• Published in: Retrovirology Vol. 10; no. 1; p. 91
• Main Authors: Kchour, Ghada, Rezaee, Rahim, Farid, Reza, Ghantous, Akram, Rafatpanah, Houshang, Tarhini, Mahdi, Kooshyar, Mohamad-Mehdi, El Hajj, Hiba, Berry, Fadwa, Mortada, Mohamad, Nasser, Roudaina, Shirdel, Abbas, Dassouki, Zeina, Ezzedine, Mohamad, Rahimi, Hossein, Ghavamzadeh, Ardeshir, de Thé, Hugues, Hermine, Olivier, Mahmoudi, Mahmoud, Bazarbachi, Ali
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.08.2013; BioMed Central
• Subjects: Adult; Aged; Analysis; Arsenic; Arsenic Trioxide; Arsenicals - administration & dosage; Bacterial infections; Blood donors; Cytokines; Cytokines - genetics; Disease; Dosage and administration; Drug therapy; Drug therapy, Combination; Female; Gene expression; Gene Expression Profiling; Health aspects; HTLV-I Infections - drug therapy; HTLV-I Infections - immunology; Human health and pathology; Human T-lymphotropic virus 1; Humans; Immunologic Factors - administration & dosage; Immunology; Infections; Infectious diseases; Interferon; Interferon-alpha - administration & dosage; Interleukins; Internal medicine; Leukemia; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Leukemia-Lymphoma, Adult T-Cell - immunology; Life Sciences; Lymphoma; Lymphomas; Male; Middle Aged; Oxides - administration & dosage; Physiological aspects; Prognosis; Prospective Studies; RNA; Statistical analysis; T cells; Thermal cycling; Treatment Outcome; Viral infections; Zidovudine; Zidovudine - administration & dosage; Beirut Lebanon; HTLV-I; Arsenic; Cytokines; ATL; Interferon; Zidovudine; Immune deficiency
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-10-91

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. 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. 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.