Macrophage- and neutrophil-dominant arthritis in human IL-1α transgenic mice
Yasuo Niki, … , Kyosuke Fujikawa, Norihiro Tada
Yasuo Niki, … , Kyosuke Fujikawa, Norihiro Tada
Published May 1, 2001
Citation Information: J Clin Invest. 2001;107(9):1127-1135. https://doi.org/10.1172/JCI11530.
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Article

Macrophage- and neutrophil-dominant arthritis in human IL-1α transgenic mice

Abstract

To study the effects of IL-1α in arthritis, we generated human IL-1α (hIL-1α). Transgenic mice expressed hIL-1α mRNA in various organs, had high serum levels of hIL-1α, and developed a severe polyarthritic phenotype at 4 weeks of age. Not only bone marrow cells but also synoviocytes from knee joints produced biologically active hIL-1α. Synovitis started 2 weeks after birth, and 8-week-old mice showed hyperplasia of the synovial lining layer, the formation of hyperplastic synovium (pannus) and, ultimately, destruction of cartilage. Hyperplasia of the synovial lining was due to the accumulation of macrophage-like cells expressing F4/80 molecules. hIL-1α was widely distributed in macrophage- and fibroblast-like cells of the synovial lining cells, as well as synovial fluid monocytes. T and B cells were rare in the synovial fluid, and analysis of marker expression suggests that synoviocytes were directly histolytic and did not act as antigen-presenting cells. In the joints of these mice, we found elevated levels of cells of the monocyte/macrophage and granulocyte lineages and of polymorphonuclear neutrophils (PMNs), most of which expressed Gr-1, indicating that they were mature, tissue-degrading PMNs. Cultured synoviocytes and PMNs from these animals overexpress GM-CSF, suggesting that the hematopoietic changes induced by IL-1 and the consequent PMN activation and joint destruction are mediated by this cytokine.

Authors

Yasuo Niki, Harumoto Yamada, Shuhji Seki, Toshiyuki Kikuchi, Hironari Takaishi, Yoshiaki Toyama, Kyosuke Fujikawa, Norihiro Tada

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Figure 4

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The histological findings of knee joints from Tg mice. Almost intact art...
The histological findings of knee joints from Tg mice. Almost intact articular cartilage with slight hyperplasia of the synovial lining layer was observed in a 2-week-old mouse (a), while destroyed cartilage was ultimately replaced by proliferative synovium, as seen in an 8-week-old mouse (b). Higher magnification of synovial fluid cells in an 8-week-old mouse shows PMN-dominant infiltration into the joint (c), cartilage/pannus junction with erosive changes in cartilage (d), and proliferation of synovial lining cells which have macrophage-like morphology (e). Magnifications: (a and b) ×50; (c) ×320; (d and e) ×200.