Naproxen and prednisolone reduced intestinal alteration and permeability and bacterial translocation in rat adjuvant-induced arthritis.

BACKGROUND

In patients with spondyloarthritis, intestinal permeability (IP) and bacterial translocation (BT) has been described as increased. Anti-inflammatory medications are known to induce deleterious intestinal changes in the general population, their effects in case of arthritis have been poorly studied.

OBJECTIVES

To assess the effect of NSAIDs and glucocorticoids on IP, BT and intestinal integrity in rats with adjuvant-induced arthritis (AIA).

METHODS

Arthritis was induced in 6-week-old male Lewis rats by injection at the base of the tail of Mycobacterium butyricum. At first signs of arthritis, rats were treated daily with naproxen, diclofenac, celecoxib, prednisolone or vehicle (saline). After 21 days of treatment, intestinal damage was determined by measure of levels of intestinal Fatty Acid Binding Protein (iFABP, ELISA), IP by measure of levels of zonulin and BT by measure of levels of soluble CD14 (sCD14, ELISA) and LPS (by liquid chromatography coupled mass spectrometry). Articular inflammation was assessed by the determination of an arthritis and radiographic score.

RESULTS

All treatments reduced and radiographic score in AIA rats (p < 0.05) compared to vehicle. In comparison with AIA, treatment with naproxen significantly reduced circulating zonulin, iFABP, LPS and sCD14 levels. Celecoxib increased zonulin but had no effect on iFABP levels. Diclofenac increased LPS levels but did not change sCD14 or iFABP levels. Prednisolone only reduced iFABP and sCD14 levels.

CONCLUSIONS

Our study is the first to demonstrate the positive effects of naproxen, a non-selective COX inhibitor and prednisolone on the intestinal barrier in a murine model of reactive arthritis-type spondyloarthritis.