Immunomodulatory Activity of Dipeptidyle Peptidase 4 Enzyme Inhibitors

Objective: To assess the immunomodulatory activity of Dipeptidyl peptidase4 inhibitors(DPP-4) on cellular and humoral immunity. DPP4 inhibitors are a relatively new class of drugs used for the treatment of diabetes.DPP4 inhibitors inhibit DPP4 enzyme. DPP4 enzyme posses immunostimulatory activity .DPP4 enzyme present on T cell surface as CD26 involve in activation of T cell, B cell, natural killer cell, DNA synthesis and release of TGF β. CD26 causes T cell proliferation by binding with adenosine diaminase (ADA) through co-stimulatory mechanism. DPP4 bind to various substrates like RANATES, IL-2, SDF-1β and 1α results in immune stimulation. Several experimental studies suggested potential role of DPP4 in various inflammatory diseases. Sitagliptin is first available DPP4 inhibitor found to be associated with intestinal cancer. On basis of above evidences evaluate immunomodulatory activity of DPP4 inhibitors if significant difference were found.
Method: In this study we evaluated immunomodulatory effect of DPP4 inhibitor by 40/80 compound induced systemic anaphylaxis in mice. In addition Inflammation induced in mice by egg albumin and arthritis induced by using Papain enzyme to evaluate anti-inflammatory activity of Sitagliptin.
Result: Sitagliptin significantly reduce motality in 40/80 compound induced anaphylactic shock in mice. Sitagliptin significantly reduce inflammation in egg induced delayed type hypersensitivity reaction. Sitagliptin significantly (p<0.01) reduce inflammation in Papain enzyme induced arthritis inflammatory model.
Conclusion: So findings of our study provide an evidence of antiallergic and anti-inflammatory activity of Sitagliptin. Therefore all observation signifies Sitagliptin posses immnosupressive effect. However further studies needed to clarify mechanism of immune suppression by Sitagliptin.