Skip to main content
  • Poster presentation
  • Open access
  • Published:

AJAK inhibitor, tofacitinibreduces IL-6 and matrix metalloproteinase-3 productionin rheumatoid arthritis with suppressed cartilage destruction


Tofacitinib, targeting Janus kiase (JAK) has gained attention as anorally available new disease modifying anti-rheumatic drug with high clinical efficacy against rheumatoid arthritis (RA). While the clinical trial has progressed and the wide usage of tofacitinib is conceivable in the near future, the precise mechanism of action in RA patients remains to be solved.

Materials and methods

Fifteen RA patients enrolled in tofacitinib clinical trial were randomized to 1, 3, 5 or 10 mg BID for 12 weeks. Serumwas collected at 0 and 12 weeks for further cytokine measurement by ELISA.To analyze the effect at the local inflammatory site, synovium and cartilage from a RA patient undergoing joint replacement was implanted to severe combined immunodeficiency (SCID) mice (SCID-huRAg mouse) andtofacitinib was administered via osmotic mini-pump and serological and histological investigation was performed.


Background of patients in clinical trial: mean age; 56.4 years, mean disease duration; 95.1 months, methotrexate (MTX) and tofacitinib were administered in all patients, median doses were 9.4 mg/week and 4.1 mg BID, glucocorticoids were administered in 6 patients, median dose was 5.4 mg/day. Baseline characteristics of the disease activity; SDAI 30.0, DAS28 (ESR) 6.3, HAQ 1.1, CRP 21.0 mg/l, ESR 57.1 mm/h, MMP-3 259.3 ng/ml, RF 216.2 U/ml. After 12 weeks treatment, disease activity decreased with statistical difference (p < 0.05) as follows; SDAI13.8, DAS28(ESR) 4.0, HAQ 0.8, CRP 8.1 mg/l, ESR 30.9 mm/h, MMP-3 149.9 ng/ml, RF 150.8 U/ml. Among the multiple cytokines measured, IL-6 and IL-8 tended to decrease, from 52.2 pg/ml to 28.2 pg/ml (p < 0.05) and from 41.7 pg/ml to 29.5 pg/ml (not significant), respectively. There was a statistically significant correlation between reduction of IL-6 and reduction of MMP-3.

In SCID-huRAg mouse, apparent invasion of RA-derived synoviuminto cartilage was observed, whileadministration of tofacitinibmarkedly suppressed invasion. In order to investigate the relevance with our findings from the patients in the clinical trial, cytokines in SCID-huRAg mouse serum was measured after administration of tofacitinib for 7 days. Interestingly, tofacitinib significantly decreased production of human IL-6 and IL-8 as well as human MMP-3 from 29.79 pg/ml to 2.89 pg/ml, 17.89 pg/ml to 4.22 pg/ml and 65.96 pg/ml to 33.13 pg/ml respectively.


Tofacitinib improved disease activity and suppressed cartilage destruction with decreased serum IL-6 and IL-8 in both, RA patients and SCID-huRAg mouse in connection with reduced MMP-3. These results indicate that tofacitinib reduces inflammation by suppressing IL-6 production and consequently inhibiting cartilage destruction in the initial several months of administration.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Yamaoka, K., Kubo, S., Sonomoto, K. et al. AJAK inhibitor, tofacitinibreduces IL-6 and matrix metalloproteinase-3 productionin rheumatoid arthritis with suppressed cartilage destruction. Arthritis Res Ther 14 (Suppl 1), P77 (2012).

Download citation

  • Published:

  • DOI: