Anti-cytokine and anti-hyperalgesic effects of aliskiren in experimental models of inflammation

INTRODUCTION The involvement of the renin-angiotensin system (RAS) in pathogenesis and progression of inflammatory responses has received much attention recently. Angiotensin II (Ang II), the main peptide of the RAS, is considered as a pro-inflammatory mediator that participates in the inflammatory response in several pathological processes.1-3 It modulates the production of adhesion molecules, cytokines (IL-6 and TNF-α), chemokines and the responses of immune and inflammatory cells, such as chemotaxis, proliferation and differentiation.4-6 Moreover, renin upregulates cytokines production acting on pro-renin receptor and independent of angiotensin II.7 In double transgenic (dTG) (harboring human renin and human angiotensinogen, R+/A+) mice, there was overexpression of human renin and human angiotensinogen, showed high levels of plasma Ang-II.8 Aliskiren inhibits the renin angiotensin system by directly inhibiting renin and subsequently decreases the production of angiotensin II. Aliskiren has been found to be beneficial in hypertension, chronic kidney disease, cardiac hypertrophy, atherosclerosis and vascular inflammation.9-11 . Various studies have also shown anti-inflammatory and antioxidant activities of aliskiren.9;12-15 Moreover, in our previous study we demonstrated analgesic activity of aliskiren in various pain models.16 Furthermore, in our previous study, analgesic activity of aliskiren was attributed to anticytokine activity in formalin induced pain model.16 Based on mentioned evidences we decided to investigate the role of renin in LPS induced inflammation in ICR, C57 and double transgenic (dTG) (harboring human renin and human angiotensinogen, R+/A+) mice and inflammatory pain in rats. Therefore, the present study was designed to explore the anti-cytokine and anti-hyperalgesic potential of aliskiren in experimental models of inflammation. Research Article