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 an 1.7 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.

• Authors: M J Janusz, S L Durham
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 46 Issue 12 Pg. 503-8 (Dec 1997) ISSN: 1023-3830 [Print] Switzerland
• PMID: 9459081 (Publication Type: Journal Article)

Chemical References

• Fluorocarbons
• Morpholines
• Oligopeptides
• Serine Proteinase Inhibitors
• MDL 101146
• Collagen
• Leukocyte Elastase

Topics

• Animals
• Arthritis (chemically induced, drug therapy)
• Arthritis, Experimental (drug therapy, pathology)
• Cartilage, Articular (pathology)
• Collagen
• Female
• Fluorocarbons
• Hindlimb (pathology)
• Leukocyte Elastase (antagonists & inhibitors)
• Morpholines (therapeutic use)
• Oligopeptides (therapeutic use)
• Rats
• Rats, Inbred Lew
• Serine Proteinase Inhibitors (therapeutic use)