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Serum macrophage migration inhibitory factor levels are correlated with response to tocilizumab therapy in patients with rheumatoid arthritis

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Abstract

To examine the relationship between serum cytokine levels and response to tocilizumab in patients with RA. The disease status of 21 RA patients was assessed at baseline and after 12 weeks of tocilizumab treatment, using the clinical disease activity index (CDAI). Clinical response to tocilizumab was defined as an improvement of >50 % from the baseline CDAI. Serum cytokine levels were quantified using double-ligand ELISA for TNF-α, IL-6, CCL2, CCL3, CXCL8, CXCL10, CX3CL1, and macrophage migration inhibitory factor (MIF). After 12 weeks of tocilizumab treatment, there was a significant overall reduction in RA disease activity (CDAI), from 22.4 ± 11.3 to 9.2 ± 6.6 (p < 0.0001), across the entire patient group. After 12 weeks of tocilizumab treatment, 14 patients achieved a >50 % improvement (the responder group), but there were no significant responses in the other 7 patients (the non-responder group). The erythrocyte sedimentation rate levels, the positive % of anti-cyclic citrullinated protein antibody and patients (%) receiving methotrexate in combination with tocilizumab were significantly higher in the responder group than in the non-responder group. Although serum baseline levels of CCL2 and CXCL8 were higher in the responder group than in the non-responder group, there were no significant changes in these chemokine levels after treatment. The serum MIF levels, but not the levels of other cytokines, in the responder group were significantly decreased after tocilizumab treatment. Our results suggest that tocilizumab differentially regulates serum cytokine profiles in patients with RA, and MIF regulation in patients with active RA may be sensitive to anti-IL-6 therapy.

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Acknowledgments

This study was supported in part by a grant from the Ministry of Health, Labor, and Welfare of Japan. We would like to thank Ms. Hiroko T. Takeuchi for her help with the experiments.

Conflict of interest

We report no conflicts of interest.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Tsuyoshi Kasama, Sakiko Isojima, Masayu Umemura, Hiroyuki Tsukamoto, Takehiro Tokunaga, Hidekazu Furuya, Ryo Yanai & Ryo Takahashi

  2. Department of Orthopedics, Showa University Northern Yokohama Hospital, Yokohama, Japan

    Masanori Nakamura

  3. Department of Orthopedics, Showa University School of Medicine, Tokyo, Japan

    Katsunori Inagaki

Authors
  1. Tsuyoshi Kasama
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  2. Sakiko Isojima
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  3. Masayu Umemura
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  4. Hiroyuki Tsukamoto
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  5. Takehiro Tokunaga
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  6. Hidekazu Furuya
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  7. Ryo Yanai
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  8. Ryo Takahashi
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  9. Masanori Nakamura
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  10. Katsunori Inagaki
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Correspondence to Tsuyoshi Kasama.

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Kasama, T., Isojima, S., Umemura, M. et al. Serum macrophage migration inhibitory factor levels are correlated with response to tocilizumab therapy in patients with rheumatoid arthritis. Rheumatol Int 34, 429–433 (2014). https://doi.org/10.1007/s00296-013-2778-0

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  • DOI: https://doi.org/10.1007/s00296-013-2778-0

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