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Abstract Number: 1469

Methotrexate Treatment Reduces Serum IL-6 Level By Decreasing a CD14brightCD16+ Intermediate Non-Classical Subset of Monocytes in RA Patients

Masako Tsukamoto1, Keiko Yoshimoto2, Noriyuki Seta3, Katsuya Suzuki2 and Tsutomu Takeuchi2, 1Division of Rheumatology, Department of Internal medicine, Keio University School of Medicine, Tokyo, Japan, 2Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 3Department of Internal Medicine, Keio university, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: IL-6, monocytes and rheumatoid arthritis (RA)

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Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose It is well known that circulating monocytes are the source of inflammatory cytokines, such as IL-6 and TNFα and newly divided into three subsets based on the expression levels of CD14 and CD16. We have previously reported that plasma IL-6 level was decreased in RA patients with clinically significant improvement after MTX treatment, but a detail mechanism is not clearly clarified. The purpose of this study is to investigate the association between three subsets of monocytes and change of serum cytokine repertoire after MTX treatment.

Methods 33 RA patients fulfilled the 2010 ACR/EULAR RA Classification Criteria and 15 healthy donors (HD) were enrolled in this study. The patients had never been received a treatment with DMARDs or biological agents and had moderate disease activity or more (DAS28-ESR ≥ 3.2). Peripheral blood samples and clinical records of the patients were obtained at the time of 0 and 12 weeks after MTX treatment. Peripheral blood samples were also obtained HD. The expression levels of CD14 and CD16 on monocytes and serum levels of cytokines were measured by flow cytometric (FACS) analysis and multiplex electrochemiluminescence assays on the Meso Scale Discovery SECTOR Imager 2400 platform®, respectively. A decrease in DAS28-ESR of 1.2 or more was defined as a clinically significant improvement after MTX treatment.

Results The mean DAS28-ESR score of the patients was 4.8 ± 0.8. There was no significant difference in clinical backgrounds between RA patients with and without improvement. Serum levels of IL-6, IL-8 and IL-10 at baseline were significantly higher in RA patients compared with HD. Only IL-6 significantly decreased in RA patients with improvement after MTX treatment. FACS analysis revealed that the proportion of CD14brightCD16+ monocytes was significantly decreased in RA patients at baseline (13.9 ± 6.9%) compared with HD (7.3 ± 2.1%) (p<0.01). After MTX therapy, the proportion of CD14brightCD16+ monocytes was significantly decreased (14.0 ± 6.5% vs 9.3 ± 5.0%, p<0.01) in RA patients with improvement, but not in those without (p=0.3). Moreover, the proportion of CD14brightCD16+ monocytes were significantly and positively correlated with serum IL-6 level and DAS28-ESR (p=0.01 and p<0.01) in RA patients.

Conclusion These results indicate that CD14brightCD16+ intermediate non-classical monocytes possibly play an important role in the pathogenesis of RA by producing IL-6 and the curative effect of MTX may be demonstrated through the reduction of CD14brightCD16+ monocytes in peripheral blood.


Disclosure:

M. Tsukamoto,
None;

K. Yoshimoto,
None;

N. Seta,
None;

K. Suzuki,
None;

T. Takeuchi,

Abbott Japan Co., Ltd., Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutica,

2,

Abbott Japan Co., Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Daiichi Sankyo Co.,Ltd.,

8,

Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Abbvie GK, Daiichi Sankyo Co.,Ltd.,

5.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-treatment-reduces-serum-il-6-level-by-decreasing-a-cd14brightcd16-intermediate-non-classical-subset-of-monocytes-in-ra-patients/

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