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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

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Combined depletion of interleukin-1 and interleukin-6 does not exceed single depletion of interleukin -1 in TNF-mediated arthritis

Silvia Hayer*, B Niederreiter, J Smolen and K Redlich

  • * Corresponding author: Silvia Hayer

Author Affiliations

Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria

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Arthritis Research & Therapy 2012, 14(Suppl 1):P44  doi:10.1186/ar3645

The electronic version of this article is the complete one and can be found online at:

Published:9 February 2012

© 2012 Hayer et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Previous studies demonstrated a regulatory role of interleukin 1 (IL-1) in inflammatory cartilage damage and bone destruction in human tumor necrosis factor transgenic (hTNFtg) mice, an animal model for Rheumatoid Arthritis (RA). Moreover, blocking of IL-6 has been shown to reduce local bone erosions in this model. Therefore we wanted to investigate the effect of a combined depletion of IL-1 and IL-6 on the development and severity of inflammatory, erosive arthritis.


We first crossed IL1α and ß deficient (IL1-/-) mice with IL6-/- mice to generate IL1-/-IL6-/- double knockout mice. We next intercrossed these animals with arthritogenic hTNFtg mice to receive IL1-/-IL6-/-hTNFtg mice. We weekly assessed clinical signs of arthritis in hTNFtg, IL1-/-hTNFtg mice, IL6-/-hTNFtg mice and IL1-/-IL6-/-hTNFtg mice starting from week 4 after birth until week 16. We stained decalcified paw sections from all 4 genotypes with hematoxylin & eosin to determine the amount of inflammatory synovial pannus formation, with tartrate-resistant acid phosphatase (TRAP) to evaluate the number of synovial osteoclasts and the occurrence of subchondral bone erosions, with toluidine-blue to assess articular cartilage damage. Quantitative analysis of histopathological changes were performed using the Osteomeasure Software System.


We found a significant reduction in the clinical signs of arthritis, indicated by an increase of paw swelling and a decrease in grip strength, in IL1-/-IL6-/-hTNFtg mice when compared to their hTNFtg littermates. In line with these findings we observed a significant decrease in synovial inflammation in IL1-/-IL6-/-hTNFtg mice when compared to hTNFtg animals. Moreover, the number of synovial TRAP+ osteoclasts was markedly diminished in IL1-/-IL6-/-hTNFtg mice and reduced osteoclast formation, was accompanied by significantly less subchondral bone erosions. Additionally, we found a conserved articular cartilage structure showing almost no cartilage degradation in IL1-/-IL6-/-hTNFtg mice compared to their hTNFtg littermates. In IL1-/-IL6-/-hTNFtg mice clinical, as well as, histological signs of disease, including joint inflammation, bone destruction and cartilage damage were also significantly diminished when compared to IL6-/-hTNFtg mice. However, by comparing IL1-/-IL6-/-hTNFtg mice with IL1-/- hTNFtg mice we found a similar reduction on synovial inflammation, as well as subchondral bone erosions and articular cartilage destruction.


The phenotype of IL1-/-IL6-/-hTNFtg mice does not differ from IL1-/-hTNFtg animals indicating no synergistic effects when IL-1 and IL-6 is simultaneously blocked in TNF-mediated arthritis.