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

Rheumatol Int. 2006 Jul;26(9):810-7. doi: 10.1007/s00296-005-0076-1. Epub 2005 Nov 15.

Abstract

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)-gamma, interleukin (IL)-2, IL-4, and tumor necrosis factor (TNF)-alpha 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-gamma and TNF-alpha significantly. There were no significant differences between the healthy volunteers and RA patients.

Conclusions: ATRA was demonstrated to affect the cytokine production of IFN-gamma and TNF-alpha. ATRA might be useful in the treatment of autoimmune diseases such as RA.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • Interferon-gamma / drug effects*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Middle Aged
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, CCR4
  • Receptors, CCR5 / drug effects
  • Receptors, CCR5 / metabolism
  • Receptors, Chemokine / drug effects
  • Receptors, Chemokine / metabolism
  • Reference Values
  • STAT6 Transcription Factor / drug effects
  • STAT6 Transcription Factor / metabolism
  • Th1 Cells / drug effects
  • Th2 Cells / drug effects
  • Tretinoin / pharmacology*
  • Tumor Necrosis Factor-alpha / drug effects*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antirheumatic Agents
  • CCR4 protein, human
  • Cytokines
  • RNA, Messenger
  • Receptors, CCR4
  • Receptors, CCR5
  • Receptors, Chemokine
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Tretinoin
  • Interferon-gamma