Physiological characterization of mBSA antigen induced arthritis in the rat. I. Vascular leakiness and pannus growth.
OBJECTIVE
To study the temporal relation between vascular inflammatory activity and synovial hyperplasia during the development of methylated bovine serum albumin (mBSA) antigen induced arthritis (AIA) in the rat, and to correlate these variables to changes in knee diameter. The influence of a single dose of indomethacin and methotrexate (MTX) on these measures was also determined.


METHODS
Vascular inflammatory activity was assessed as extravasation of radiolabelled albumin. Synovial hyperplasia was followed by measurements of the increases in wet and dry weight of the anterior part of the periarticular soft tissue and by routine histology.


RESULTS
The vascular inflammation peaked on Day 3 after antigen challenge. The pannus weight increased at a slower pace, peaking on Day 7. No major difference between the sexes was found in these responses. Both variables were attenuated by MTX or indomethacin, suggesting a dependence between them. The water content of the pannus increased in tandem with the tissue growth but did not correlate to vascular leakiness, and is thus explained by the structural properties of the pannus rather than by the formation of inflammatory edema. In histological sections, ingrowth of pannus and destruction of cartilage was visible from Day 3 until the end of the experiment.


CONCLUSIONS
Proliferative response follows the inflammatory vascular inflammation over time. The knee diameter, which is the most commonly used clinical measurement, seems mainly to be a reflection of the former variable. The effects of MTX and indomethacin suggest that the pannus formation is induced by the inflammatory activity in this model.
Andersson
S E
SE
Department of Pharmacology, Preclinical Research and Development, Astra Draco AB, Lund, Sweden.
Lexmüller
K
K
Ekström
G M
GM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001168:Arthritis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D051381:Rats; D012710:Serum Albumin, Bovine; D013583:Synovial Membrane / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D007213:Indomethacin; D008727:Methotrexate