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Effect of prednisolone and saireito co-administration on T-cells of rheumatoid arthritis patients


1, 2, 3, 4, 5, 6, 7

 

  1. Department of Drug Safety and Risk Management, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. y141193@toyaku.ac.jp
  2. Department of Drug Safety and Risk Management, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
  3. Department of Drug Safety and Risk Management, Tokyo University of Pharmacy and Life Sciences, and Division of Pharmacoepidemiology, Department of Healthcare and Regulatory Sciences, Showa University School of Pharmacy, Tokyo, Japan.
  4. Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
  5. Department of Rheumatology, Tokyo Medical University Hospital, Tokyo, Japan.
  6. Department of Rheumatology, Tokyo Medical University Hospital, Tokyo, Japan.
  7. Department of Drug Safety and Risk Management, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

CER16156
2023 Vol.41, N°9
PI 1777, PF 1783
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PMID: 36826781 [PubMed]

Received: 25/08/2022
Accepted : 16/12/2022
In Press: 24/02/2023
Published: 17/08/2023

Abstract

OBJECTIVES:
Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the risk of osteoporosis and osteonecrosis. Saireito (114) can be used to reduce PSL dose owing to its immunosuppressive effects. However, the effect of combination therapy of PSL+114 on the immune system of RA patients remains unknown. This study compared the effect of PSL alone and PSL+114 on peripheral blood mononuclear cell (PBMC) proliferation, T-cell subsets, and cytokine production in adult RA patients receiving MTX monotherapy.
METHODS:
We isolated PBMCs from 14 consenting RA patients, and cultured them with PSL (0.0001–1.0 μM) in combination with or without 114 (300 μg/mL) for 96 h in the presence of concanavalin A. We measured the proliferation rates of PBMC, proportions of CD4+, CD8+, and CD4+CD25+Foxp3+T-cells (induced T-regulatory cells), and concentrations of interferon-γ, interleukin (IL)-6, IL-10, IL-17A, and tumour necrosis factor in the culture supernatant.
RESULTS:
Compared to the blank, the PBMC proliferation rate significantly decreased at a reduced PSL concentration after 114 administration. The 50% inhibition concentration was 0.43 μM PSL for the PSL-only group as compared to 0.29 μM PSL for the PSL+114 co-administration group. The PSL+114 co-administration group had a significantly higher concentration of IL-6 compared to the PSL-only group.
CONCLUSIONS:
The use of 114 in combination with low-concentration PSL intensified its immunosuppressive effect. However, the concentration of IL-6 was elevated in the co-administration group, suggesting exacerbation of RA activity.

DOI: https://doi.org/10.55563/clinexprheumatol/ohcf0k

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