Date: Monday, November 9, 2020
Session Type: Poster Session D
Session Time: 9:00AM-11:00AM
Background/Purpose: The gut is no longer considered as a simple element associated with spondyloarthritis but as a real actor of the disease. In patients with spondyloarthritis, the presence of intestinal inflammation and an increase in digestive permeability responsible for bacterial translocation has been described. No data are available on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on this bacterial translocation in patients with spondyloarthritis. Zonulin and lipopolysaccharide (LPS) have been described as good biomarkers of intestinal permeability and bacterial translocation, respectively. Adjuvant-induced arthritis (AIA) is a model of recent arthritis characterized by ossification and ankylosis in the post arthritis period. This model can be considered as a model of reactive arthritis in which our previous work has reported a clear efficacy of NSAIDs with differences between molecules at the structural and vascular levels.To test the hypothesis that there is an increase in digestive permeability and bacterial translocation in the AIA model and to show the influence of different NSAIDs on these two parameters.
Methods: Adjuvant-induced arthritis (AIA) was induced in 6-week-old male Lewis rats by an injection at the base of the tail of Mycobacterium butyricum in incomplete Freund’s adjuvant. A group of non-AIA (control) rats received saline. At the first signs of arthritis, the AIA-rats were evaluated (arthritis score 0-6) and treated daily intraperitoneally with naproxen (10 mg/kg/day), diclofenac (5mg/kg twice daily), celecoxib (3 mg/kg/day) or saline solution (AIA-vehicle group). After 21 days of treatment, the rats were sacrificed and serum levels of zonulin and LPS were evaluated by ELISA and liquid chromatography-mass spectrometry, respectively. Circulating levels of TNF-α and IL1-β were measured as well as the hind paw radiographic score.
Results: Compared to the control group, there was a significant increase in zonulin concentration ( p < 0.001) in the AIA group. There was no significant difference in the concentration of LPS between the two groups. The levels of zonulin were correlated with the TNF-α levels (R= -0.42; p=0.032) and the arthritis score (R=0.45; p=0.013) but not with the level of IL1-β (R=; p-0.018; p=0.39). Treatment with NSAIDs significantly and equivalently decreased the arthritis score in each group. Compared to the vehicle group, treatment with naproxen significantly decreased the radiographic score (p< 0.001), TNF-α, IL1-β (p < 0.01), zonulin (p< 0.001) and LPS (p < 0.05). Celecoxib decreased radiographic score (p < 0.001), IL1-β (p < 0.01), TNF-α (p < 0.01) but increased zonulin levels (p < 0.05) without effect on LPS. Diclofenac also decreased radiographic score (p < 0.001), TNF-α (p < 0.01), and IL1-β (p < 0.01) but increased both zonulin (p < 0.01) and LPS (p < 0.001).
Conclusion: We have demonstrated an increase in serum zonulin levels in the AIA model and a beneficial effect of naproxen on intestinal permeability and bacterial translocation in contrast to celecoxib and diclofenac. Moreover, the plasmatic zonulin levels were correlated with TNF-α but not with IL1-β supporting a pivotal role of TNF-α on the tight junctions in this model.
To cite this abstract in AMA style:Hecquet S, Bordy R, Prati C, Wendling D, Demougeot C, Verhoeven F. Intestinal Permeability in the Adjuvant Induced Arthritis Model: Preliminary Study and Impact of NSAIDs [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/intestinal-permeability-in-the-adjuvant-induced-arthritis-model-preliminary-study-and-impact-of-nsaids/. Accessed May 15, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/intestinal-permeability-in-the-adjuvant-induced-arthritis-model-preliminary-study-and-impact-of-nsaids/