Rheumatology International

, Volume 26, Issue 9, pp 810–817

All-trans-retinoic acid suppresses interferon-γ and tumor necrosis factor-α; a possible therapeutic agent for rheumatoid arthritis

  • Yuji Nozaki
  • Chise Tamaki
  • Toshiaki Yamagata
  • Masafumi Sugiyama
  • Shinya Ikoma
  • Koji Kinoshita
  • Masanori Funauchi
Original Article


Objectives: To study the effects of all-trans-retinoic acid (ATRA), we determined the proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) and CD4+ T cells in healthy volunteers and patients with rheumatoid arthritis (RA), and explored the possibility of using ATRA as a therapeutic agent for autoimmune diseases. Methods: Proliferation of these cells was determined by modified MTT assay, and expression of CC chemokine receptors 4 (CCR4) and CCR5 was determined by flow cytometry. Production and expression of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and tumor necrosis factor (TNF)-α was determined by Enzyme-Linked Immunosorbent Assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). The presence of STAT6 protein was determined by Western blot analysis. Results: ATRA did not affect the proliferation or production of IL-2 and IL-4. We did not detect STAT6 protein, and saw no evidence of the differentiation of PBMCs to Th1 or Th2 cells. In contrast, ATRA suppressed the production of IFN-γ and TNF-α significantly. There were no significant differences between the healthy volunteers and RA patients. Conclusions: ATRA was demonstrated to affect the cytokine production of IFN-γ and TNF-α. ATRA might be useful in the treatment of autoimmune diseases such as RA.


Th1/Th2 cells Cytokine All-trans-retinoic acid Autoimmune disease 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Yuji Nozaki
    • 1
  • Chise Tamaki
    • 1
  • Toshiaki Yamagata
    • 1
  • Masafumi Sugiyama
    • 1
  • Shinya Ikoma
    • 1
  • Koji Kinoshita
    • 1
  • Masanori Funauchi
    • 1
  1. 1.Department of Nephrology and RheumatologyKinki University School of MedicineOsakaJapan

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