Cyclosporine a and Cyclophilin a with Probiotics in the Management of Inflammatory Bowel Diseases in Syndecan-1 Knock out Mice

Abstract Body : Background: Inflammatory Bowel Diseases constitute a group of refractory autoimmune disorders. Their treatment modalities have evolved over the years to include immunoregulators like cyclosporine A, an immunosuppressant that interacts with cytoplasmic cyclophilin A.
Aims: To explore the role of Syndecan-1 knock out mice in the IBD pathogenic process and the effectiveness of cyclophilin A and cyclosporine A in the management of IBD in presence of probiotics.
Materials and Methods: IBD was induced in a total of 112 mice equally divided between Syndecan-1 knock out and Balb/c mice; using 2% DSS for a week followed by 2 weeks of treatment with 200µg every other day cyclosporine A and 25µg per day cyclophilin A, intraperitoneally. In addition, a daily dose of 108CFU of a combination of probiotics in drinking water.
Animals were monitored for 3 weeks for signs and symptoms. Sigmoid colon biopsies were removed for routine microscopy as well as frozen for protein extraction and molecular testing of IL-6, CD3, CD147, Beta-1 integrins and pAkt expression.
Results: The induction of IBD in the Syndecan-1 knock out mice was more sever at clinical, histologic and molecular levels than in the wild type with a higher DAI index and more sever intestinal histological alterations. Separate treatment with cyclophilin A or cyclosporine A showed more inhibition of IL-6 in the wild type but no added inhibitory effect when administered as a combination together. Probiotics added to the combination were more effective in the wild type and when used alone its inhibition of IL-6 was the highest especially in the wild type.
As for the CD147, CD3, IL-6, Beta-1 integrins and pAkt markers there were more suppressions across the various groups in both strains but more in knock out mice. On the other hand, the combination led to a rise in expression of CD147 compared to either CyA or CypA alone in the KO mice, an exacerbation. However, when probiotics was added to the combination, it had little if any effect in the KO. Probiotics alone significantly decreased expression of the inflammation markers in both strains. However, the CypA-CyA complex increased significantly CD3, CD147, Beta-1 integrins and pAkt expressions and led to more inflammation in knock out mice.
Conclusion: In comparison to the wild type, the inflammation was more sever in the KO mice, and treatment with CyA led to more reduction in inflammation and more suppression of expression of inflammation markers. Probiotics added to the CypA-CyA, had little effect in KO but more effect in the wild type to decrease inflammation which was exacerbated. Probiotics used alone ameliorated the inflammation in both strains. The differential effects of various treatments on inflammatory markers, histological alterations, and clinical signs and symptoms speak in favor of a possible role of Syndecan-1, CyA in IBD treatment. However, probiotics need to be considered after more explorations on the mechanisms involved.