Lymphoblastoid interferon-alpha inhibits T cell proliferation and expression of eosinophil-activating cytokines

J Interferon Cytokine Res. 1996 Oct;16(10):819-27. doi: 10.1089/jir.1996.16.819.

Abstract

T cell-derived cytokines, such as interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) activate eosinophils, whereas other cytokines, such as tumor necrosis factor (TNF)-alpha and IL-13, determine eosinophil recruitment. Interferon-alpha (IFN-alpha), a leukocyte-derived cytokine, has been shown to have beneficial effects in eosinophil-mediated disorders, such as the hypereosinophilic syndrome and a murine model of allergic asthma, where it inhibited eosinophil recruitment. We tested the hypothesis that IFN-alpha acted in eosinophil-mediated disorders by modulating T cell cytokine expression. Peripheral blood mononuclear cells (PBMC) or human ragweed-specific TH1 (2B8) and TH2 (2D2) T cell clones were cultured in the presence of 5 micrograms/ml of phytohemagglutinin (PHA) or 25 micrograms/ml of antigen Amb a 1 (short ragweed allergen), respectively, and lymphoblastoid IFN-alpha (varying from 0 to 10,000 U/ml). We assessed T cell proliferation by [3H]thymidine incorporation and production of IL-5 and GM-CSF by ELISA. Expression of cytokine transcripts was analyzed by the reverse transcription-polymerase chain reaction technique (RT-PCR). IFN-alpha induced a dose-dependent suppression of T cell proliferation of both PBMC (p < 0.001) and the T cell clones (p < 0.001). IFN-alpha inhibited gene expression of IL-5, GM-CSF, TNF-alpha, and IL-13 in PBMC. Furthermore, IFN-alpha significantly inhibited mitogen-induced and antigen-induced production of IL-5 and GM-CSF. IFN-alpha may benefit eosinophil-mediated disorders by inhibiting T cell function and production of cytokines active on human eosinophils.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cell Division / drug effects
  • Cells, Cultured
  • Clone Cells
  • Cytokines / genetics
  • Cytokines / pharmacology*
  • Eosinophils / drug effects*
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interleukin-13 / pharmacology
  • Interleukin-5 / pharmacology
  • Leukocytes, Mononuclear / metabolism*
  • Middle Aged
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Interferon-alpha
  • Interleukin-13
  • Interleukin-5
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor