- Paper Report
- Open Access
Arthritis in TNF-deficient mice
- Cheryl Smythe1
© Biomed Central Ltd 2001
- Received: 13 July 2001
- Published: 27 July 2001
- Collagen-induced arthritis
- mBSA/IL-1-induced arthritis
Tumour necrosis factor (TNF) is thought to play a pivotal role in mediating the cytokine cascade that results in rheumatoid arthritis (RA). Although an overproduction of TNF is observed in RA and inhibition of TNF attenuates experimental arthritis, the absolute dependency of inflammatory arthritis on TNF remains to be determined. To address this issue, the authors have examined the effect of TNF deficiency in two models of RA: collagen-induced arthritis (CIA) and methylated BSA (mBSA)/IL-1-induced arthritis.
The overall incidence and severity of CIA in TNF-deficient mice (on a B6 background) was not significantly different compared to that in wild-type mice. Histologic analysis suggested fewer severely involved joints in the TNF-deficient mice. Importantly, some mice in both groups developed severe CIA. In the TNF-deficient mice, the IgG response to type II collagen (CII) was significantly reduced, while the IgM response was comparable to that in wild-type mice. In vitro lymph node cell proliferation was unaltered, but interferon (IFN)-? levels were significantly elevated in the knockout mice in response to CII. All TNF-deficient mice developed lymphadenopathy and splenomegaly in response to CII immunisation, with an increase in all leukocyte populations in the inguinal lymph nodes of knockout compared to wild-type mice. In particular there was a significant increase in CD4+ memory T cells. The TNF-deficient mice also developed severe acute inflammatory arthritis in response to intra-articular mBSA injection, although the incidence of inflammatory or destructive arthritis was lower in the TNF-deficient mice compared to controls. In the synovium at day 7, levels of mRNA for IL-1a, IL-1?, IL-1 receptor antagonist, IL-18, IL-6, IFN-? and macrophage inhibitory factor differed little between knockout and wild-type animals.
TNF-deficient mice, ELISA, T-cell proliferation assay, immunohistochemistry, flow cytometry, RNase protection analysis, mBSA/IL-1-induced arthritis and collagen-induced arthritis models
There are two recent commentaries on the role of anti-cytokine therapy in the treatment of arthritis.
Brennan F: A follow-up to "Anti-cytokine therapy in chronic destructive arthritis" by Wim B van den Berg. Arthritis Res 2001, 3:211-213 (PubMed abstract).
van den Berg WB: Response to Fionula Brennan's commentary "A follow-up to 'Anti-cytokine therapy in chronic destructive arthritis" by Wim van den Berg." Arthritis Res 2001, 3:214-215 (PubMed abstract).
And another recent paper report on the following article focuses on the roles of IL-1a and TNF in arthritis.
Niki Y, Yamada H, Seki S, Kikuchi T, Takaishi H, Toyama Y, Fujikawa K, Tada N: Macrophage- and neutrophil-dominant arthritis in human IL-1a transgenic mice. J Clin Invest 2001, 107:1127-1135 (Paper report).