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Rheumatology Advance Access published online on January 3, 2008
Rheumatology, doi:10.1093/rheumatology/kem344
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Effectiveness of etanercept in bleomycin-induced experimental scleroderma

S. S. Koca1, A. Isik1, I. H. Ozercan2, B. Ustundag3, B. Evren1 and K. Metin3

1Department of Rheumatology, 2Department of Pathology and 3Department of Biochemistry, Faculty of Medicine, Firat University, Elazig, Turkey.

Correspondence to: S. S. Koca, Firat University, Firat Tip Merkezi, Ic Hastaliklari AD./Romatoloji BD., 23119-Elazig, Turkey. E-mail: kocassk{at}yahoo.com


  Abstract

Objectives. To evaluate the effects of etanercept and thalidomide in the mouse model of bleomycin-induced scleroderma (BLM-IS).

Methods. This study involved four groups (n = 8 mice in each group). Dermal sclerosis was induced by repeated subcutaneous injections of BLM (10 µg) for 4 weeks in BALB/c mice. Control group received only phosphate-buffered saline. The second group received only BLM; the third and fourth groups were also given an intraperitoneal injection of 100 µg etanercept or 150 mg/kg thalidomide, respectively.

Results. BLM increased serum TGF-β1, tissue hydroxyproline levels and expression of {alpha}-smooth muscle actin ({alpha}-SMA), and dermal fibrosis was histopathologically prominent. Although thalidomide had no significant effect, etanercept caused decreases in levels of serum TGF-β1, tissue hydroxyproline and number of {alpha}-SMA-positive cells.

Conclusion. Inhibition of TNF-{alpha} with etanercept in BLM-IS was resulted in a significant reduction of the dermal sclerosis, collagen accumulation and the number of infiltrating myofibroblastic cells. TNF-{alpha} may play a key role in the progression of BLM-IS and TNF-{alpha} antagonists may be useful in the management of scleroderma.

KEY WORDS: Scleroderma, Bleomycin, Etanercept, Animal model

Submitted 25 July 2007; revised version accepted 19 November 2007.
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