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

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.