Τίτλος:
Attenuation of inflammatory polyarthritis in TNF transgenic mice by
diacerein: comparative analysis with dexamethasone, methotrexate and
anti-TNF protocols
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The impact of diacerein, an effective cartilage targeted therapy that is
used in patients with osteoarthritis, on the development and progression
of chronic inflammatory arthritis was evaluated in a tumor necrosis
factor (TNF) transgenic mouse model (Tg197). The response to diacerein
at 2, 20, or 60 mg/kg daily, as well as the comparative effects of other
antiarthritis drugs including dexamethasone (0.5 mg/kg daily),
methotrexate ( 1 mg/kg three times weekly) and an anti-TNF agent ( 5
mg/kg weekly), were assessed in the Tg197 mice. Treatment was initiated
before the onset of arthritis and was continued for 5 weeks. A
significant improvement in clinical symptoms was found in all three
diacerein treated groups in comparison with untreated groups. Confirming
these data, semiquantitative histopathologic analysis of the hind paws
revealed a significant reduction not only in cartilage destruction but
also in the extent of synovitis and bone erosion in diacerein treated
groups in comparison with untreated groups. At the most effective dose
tested ( 2 mg/kg daily), diacerein inhibited the onset of arthritis in
28% and attenuated the progression of arthritis in 35% of the Tg197
mice. Comparative analyses showed diacerein to be more potent than
methotrexate but not as effective as dexamethasone or anti-TNF agents in
suppressing the progression of the TNF mediated arthritis in this model.
These results indicate that diacerein has a disease modifying effect on
the onset and progression of TNF driven chronic inflammatory arthritis,
suggesting that the prophylactic or therapeutic potential of diacerein
in patients with RA should be further examined.
Συγγραφείς:
Douni, E
Sfikakis, PP
Haralambous, S
Fernandes, P and
Kollias, G
Περιοδικό:
Arthritis Research and Therapy
Λέξεις-κλειδιά:
arthritis; diacerein; inflammation; transgenic; tumor necrosis factor
