Reciprocal influence of experimental arthritis on colitis: a model to study extraintestinal manifestations of IBD?
Abstract
Introduction: Inflammatory bowel diseases (IBD), including Crohn’s disease
(CD) and ulcerative colitis (UC), are systemic inflammatory diseases affecting
200 000 people in France and overall 3 million people across Europe [1].
Extraintestinal manifestations (EIM) occur frequently in IBD patients [2].
Amongst these associated complications, rheumatologic manifestations are the
most frequent. Conversely, gut inflammation is present in approximately twothirds
of patients with spondyloarthritis [3]. Understanding the mechanisms
underlying the development of such complications in IBD is a prerequisite to
improving the management of these patients. Aim of this study was to investigate
influence of experimental colitis on arthritis and vice versa.
Material and methods: DSS-induced colitis and collagen-induced arthritis
(CIA) were concomitantly induced in DBA/1J mice. Briefly, at day 0, arthritis
was induced by intradermal injection of type II bovine collagen, and colitis
was performed between day 14 and day 21 with DSS dissolved in drinking
water. Mice were daily weighed and severity of arthritis was graduated using
macroscopic arthritic score and quantified by measuring hindpaws oedema by
plethysmography. Colitis severity was evaluated by disease activity index
(DAI) and by detection of fecal lipocalin-2 measured by ELISA. At day 41,
mice were sacrificed and histological analyzes were realized in intestines and
ankles.
Results: Clinical parameters showed that induction of colitis during arthritis
development delayed disease onset (2 1 day of delay) and reduced its severity
(5.75 1.62 in arthritis only group vs. 4.00 1.48 in arthritis + colitis group).
Preliminary histological analyses confirmed these observations. Finally, fecal
lipocaline-2 was reduced (50%-decrease) in animal suffering from arthritis and
colitis when compared to mice with colitis only.
Discussion/Conclusion: These preliminary results indicate that concomitant
experimental colitis could influence arthritis in mice and vice versa as demonstrated
by reduction of disease severity index and fecal lipocalin 2.
References:
[1] Bourikas LA. and Papadakis KA. Inflamm Bowel Dis. (2009) 15, 1915–
1924.
[2] Leclerc-Jacob S. and al. Aliment Pharmacol Ther. (2014) 39, 957–962.
[3] Van Praet L. and al. Nat Rev Rheumatol. (2012) 8, 288–295.