title: The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.
abstract: 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.
authors: Department of Biology, Faculty of Sciences, Lebanese University, Hadath, Lebanon.
authors: Ghada
authors: G
authors: Kchour
authors: Rahim
authors: R
authors: Rezaee
authors: Reza
authors: R
authors: Farid
authors: Akram
authors: A
authors: Ghantous
authors: Houshang
authors: H
authors: Rafatpanah
authors: Mahdi
authors: M
authors: Tarhini
authors: Mohamad-Mehdi
authors: MM
authors: Kooshyar
authors: Hiba
authors: H
authors: El Hajj
authors: Fadwa
authors: F
authors: Berry
authors: Mohamad
authors: M
authors: Mortada
authors: Roudaina
authors: R
authors: Nasser
authors: Abbas
authors: A
authors: Shirdel
authors: Zeina
authors: Z
authors: Dassouki
authors: Mohamad
authors: M
authors: Ezzedine
authors: Hossein
authors: H
authors: Rahimi
authors: Ardeshir
authors: A
authors: Ghavamzadeh
authors: Hugues
authors: H
authors: de Thé
authors: Olivier
authors: O
authors: Hermine
authors: Mahmoud
authors: M
authors: Mahmoudi
authors: Ali
authors: A
authors: Bazarbachi
mesh_terms: D000328:Adult; D000368:Aged; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015490:HTLV-I Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D016898:Interferon-alpha / Q000008:administration & dosage*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D001152:Arsenicals; D016207:Cytokines; D007155:Immunologic Factors; D016898:Interferon-alpha; D010087:Oxides; D015215:Zidovudine; D000077237:Arsenic Trioxide
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