Increased IL-10/IL-17 ratio is aggravated along with the prognosis of patients with chronic lymphocytic leukemia

Int Immunopharmacol. 2016 Nov:40:57-64. doi: 10.1016/j.intimp.2016.07.008. Epub 2016 Aug 29.

Abstract

Objective: This study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL).

Methods: Totally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR.

Results: Treg and Th17 cell proportions in peripheral blood in the CLL patients were significantly higher than control. Serum levels of IL-10 and IL-17, and expression of Foxp3 and RORγt, were significantly increased in the CLL patients. Ratios of Treg/Th17 and IL-10/IL-17 were significantly elevated in the CLL patients. Compared with those before treatment, Treg/Th17 and IL-10/IL-17 ratios were declined in the CLL patients in remission. Compared with the non-remission group, Treg cells were significantly decreased, while Th17 cells were significantly increased, resulting in decreased Treg/Th17 ratio, in the remission group. Moreover, the serum IL-10 level was significantly decreased, while the serum IL-17 level was significantly increased, resulting in declined IL-10/IL-17 ratio, in the remission group. Correlation analysis showed that, Treg and Th17 cell counts were significantly associated with CD38 and ZAP-70 expression in the CLL patients. Moreover, the IL-10/IL-17 ratio was also significantly associated with CLL prognostic factors.

Conclusion: Altered Treg/Th17 and IL-10/IL-17 ratios in CLL would be aggravated along with the disease progression, which might be used as indicators for the disease prognosis.

Keywords: Chronic lymphocytic leukemia (CLL); IL-10; IL-17; Regulatory T (Treg) cells; Th17 cells.

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Chlorambucil / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Female
  • Forkhead Transcription Factors / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-10 / blood*
  • Interleukin-17 / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Prognosis
  • Rituximab / therapeutic use
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Antineoplastic Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • Immunosuppressive Agents
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Interleukin-10
  • Chlorambucil
  • Rituximab
  • Cyclophosphamide
  • Vidarabine
  • fludarabine