Inhibition of cartilage degradation in rat collagen-induced arthritis but not adjuvant arthritis by the neutrophil elastase inhibitor MDL 101,146

Abstract.

Objective and Design: The neutrophil elastase inhibitor MDL 101,146 was examined for its anti-arthritic effect and to determine the role of neutrophil elastase in collagen-induced arthritis and adjuvant arthritis.¶Material: The collagen-induced arthritis model was performed in female DA rats immunized on day 0 and 7 with chick type II collagen in Freund's incomplete adjuvant. Adjuvant arthritis was induced in female Lewis rats by an intradermal injection of heat-killed Mycobacterium tuberculosis H37RA.¶Methods: The clinical signs of arthritis were assessed, joint swelling was measured using calipers and bone degradation, new bone proliferation, pannus formation and cartilage degradation were evaluated histologically.¶Results: MDL 101,146 administered orally inhibited the severity of collagen-induced arthritis as measured by a reduction in clinical score and joint swelling. Histological evaluation demonstrated a bone and cartilage sparing effect of MDL 101,146 in the tibio-tarsal joint of animals with collagen-induced arthritis.¶Conclusions: These results suggest that destruction of the joint in collagen-induced arthritis is at least partially due to neutrophil elastase.