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Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics

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Abstract

The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-γ, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-α in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA.

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Acknowledgements

We thank Associate Professor Somrat Lertmaharit, Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, for statistical consultation; Ms. Chaweewan Punkum and Ms. Duangporn Emampaiwong, Bio-Rad Laboratories, Ltd., Bangkok, Thailand, for performing multiplex cytokine assays and technical assistance; and Professor Robert J. Moots, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK, for scientific consultation and critical review of the manuscript.

Authors’ contributions

MO initiated the concept and design of the study; collected, analyzed, and interpreted the data; prepared the manuscript; and finalized it according to the recommendations. JW initiated the study design, analyzed and interpreted the data, and critically revised the manuscript. YS cleaned the raw data, entered the cleaned data to SPSS program,analyzed the data, and created all of the figures. NT acquired the laboratory data and tested them for accuracy and integrity and interpreted the laboratory data. All of the authors read and approved the entire content of the submitted manuscript.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, 10330, Thailand

    Manathip Osiri

  2. Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Jongkonnee Wongpiyabovorn

  3. Department of Public Health Administration, Faculty of Public Health, Mahidol University, Bangkok, Thailand

    Youwanuch Sattayasomboon

  4. Division of Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Niramol Thammacharoenrach

Authors
  1. Manathip Osiri
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  2. Jongkonnee Wongpiyabovorn
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  3. Youwanuch Sattayasomboon
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  4. Niramol Thammacharoenrach
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Corresponding author

Correspondence to Manathip Osiri.

Ethics declarations

This study was approved by Chulalongkorn University Institutional Review Board (study IRB number 533/56).

Funding

This study was funded by Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number RA 57/072. The funding body had no influence on the design, analysis, or results reported of this study.

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Osiri, M., Wongpiyabovorn, J., Sattayasomboon, Y. et al. Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics. Clin Rheumatol 35, 1673–1681 (2016). https://doi.org/10.1007/s10067-016-3306-x

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  • DOI: https://doi.org/10.1007/s10067-016-3306-x

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