Effectiveness of etanercept in bleomycin-induced experimental scleroderma.
OBJECTIVE
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 microg) 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 microg etanercept or 150 mg/kg thalidomide, respectively.


RESULTS
BLM increased serum TGF-beta1, 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-beta1, tissue hydroxyproline and number of alpha-SMA-positive cells.


CONCLUSIONS
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.
Koca
S S
SS
Department of Rheumatology, Faculty of Medicine, Firat University, Elazig, Turkey. kocassk@yahoo.com
Isik
A
A
Ozercan
I H
IH
Ustundag
B
B
Evren
B
B
Metin
K
K
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001761:Bleomycin; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D000068800:Etanercept; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012594:Scleroderma, Localized / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D001761:Bleomycin; D000068800:Etanercept; D006909:Hydroxyproline