AB0111 EFFECT OF TOFACITINIB AND GLUCOCORTICOIDS ON INTESTINAL PERMEABILITY, EPITHELIAL DAMAGE AND BACTERIAL TRANSLOCATION IN RAT ADJUVANT-INDUCED ARTHRITIS

Abstract

BackgroundGrowing evidence indicated that the intestine is not only a target but also an actor of the pathogenesis in chronic inflammatory rheumatic diseases (CIRD). Consistently, increased intestinal permeability (IP) and damage (ID) as well as bacterial translocation (BT) have been described in patients with CIRD. However, the effects of treatments used in patients with CIRD on gut health are unknown.ObjectivesTo determine the effect of glucocorticoids (GCs) and tofacitinib on IP, ID and BT in rats with adjuvant-induced arthritis (AIA).MethodsAIA was induced in 6-week-old male Lewis rats by a tail injection of Mycobacterium butyricum in incomplete Freund’s adjuvant. At onset of arthritis, rats were treated daily with prednisolone at low (0.1 mg/kg/day, i.p.) or high dose (10 mg/kg/day, i.p.), or with Tofacitinib (10 mg/kg twice a day, s.c.) or with vehicle. After 21 days, IP, ID and BT were assessed by measurement of plasma levels of zonulin, intestinal Fatty Acid Binding Protein (iFABP) and serum levels of soluble CD14 (sCD14) by ELISA), respectively. Arthritis severity was daily evaluated through the determination of an arthritis score.ResultsCompared to vehicle, Tofacitinib and high-dose of GC both reduced arthritis score (p<0.001) and levels of sCD14 (-44%, p<0.001 and -41% p<0.001 respectively) in AIA. High dose of GC decreased iFABP (-17%, p<0.05) levels but had no effect on zonulin levels. Tofacitinib did change nor iFABP neither zonulin levels. As compared to vehicle, the low-dose of GC had no effect on arthritis severity, sCD14, iFABP and zonulin plasma levels.ConclusionPrednisolone at a dose efficient on arthritis did not worsen but on the contrary reduced intestinal bacterial translocation and epithelial damage. These results are consistent with the positive effects of GCs on intestinal dysfunction observed in case of sepsis or colitis. The lack of efficacy of the sub-therapeutic dosage of prednisolone suggested that effects of GC are, at least partly, related to their anti-inflammatory effects. Consistent with the positive effect of jakinibs in patients with inflammatory bowel disease, Tofacitinib blunted intestinal bacterial translocation in AIA. Given the suspected pathophysiological link between bacterial translocation and arthritis, our results identified a new mechanism involved in the positive effects of GC and tofacitinib in arthritis diseases.Disclosure of InterestsNone declared