In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 56.6-56.6
Abstract:
Rheumatoid Arthritis is characterized by chronic inflammation and synovial hyperplasia which leads to the destruction of cartilage and bone. We have shown earlier (Wu et al, 2007) that blocking IL1α/β provides better efficacy than monotherapy in a CIA model when treatment begins at first clinical sign of inflammation but not necessarily bone loss (therapeutic mode). These studies describe a late therapeutic mCIA treatment mode designed to evaluate the efficacy of anti-inflammatory drugs on inflammation and bone in animals with established bone lesions. To define the kinetics of bone loss, male DBA1/J mice with established arthritis were sacrificed at days 5, 7, 9 and 11 after onset of first clinical signs of disease. Day 7 was selected as the optimal point to begin treatment based on 28% decrease in tarsal bone volume and 27% increase in erosion by microCT and correlating bone histomorphometry endpoints. The efficacy of two pairs of anti-inflammatory mAbs was evaluated: 1) Anti-TNF alone and in combination with anti-PGE2 and 2) anti-IL1β alone and in combination with anti-IL1α. Treatment was initiated on day 7 and was continued for 2 weeks. For both antibody sets, the paired combination significantly reduced inflammation (by 40%) and maintained bone volume to a greater extent than anti-TNF or anti-IL1β dosed alone (37% and 22% increase). Our data demonstrate that a late therapeutic mCIA mode can be used to evaluate effects of anti-inflammatory drugs on bone loss.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.56.6
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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