Effects of conivaptan and mannitol on serum cytokine levels (TNF-α, IL-15 and IL-35) following bilateral carotid artery occlusion

This study was aimed to investigate the post-ischemic effects of aquaretic conivaptan and diuretic mannitol on serum tumor necrosis factor-α (TNF-α), interleukin-15 (IL-15) and interleukin-35 (IL-35) levels in an experimental cerebral ischemia-reperfusion (I/R) rat model. Healty male Sprague-Dawley rats were randomly divided into five groups: Control (Sham), I/R (I/R+Saline), MAN (I/R+mannitol), CON10 (I/R+conivaptan 10 mg/ml), and CON20 (I/R+conivaptan 20 mg/ml). Cerebral ischemia was conducted using bilateral common carotid artery occlusion technique. At the onset of reperfusion, saline, conivaptan or mannitol were administrated intravenously. The blood samples were taken at 6th hours of reperfusion. Rat serum TNF-α, IL-15 and IL-35 levels were measured by using commercial ELISA Kits. The biochemical analyses showed that I/R method led to an increase in serum TNF-α and IL-15 levels when compared with the control. Conivaptan treatments decreased TNF-α and IL-15 levels significantly compared to the I/R group (p<0.001). IL-35 levels were high in all ischemia groups, but 10 mg/ml conivaptan brought its levels close to the control (p<0.001). The results of Spearman’s correlation analyses showed that serum TNF-α levels were positively correlated with IL-15 levels (p<0.001, r=0.596) and IL-35 levels (p<0.05, r=0.319). According to our findings on pro-inflammatory and anti-inflammatory cytokine levels, conivaptan was dose-dependently more effective than mannitol in balancing inflammatory response. This study may provide useful information in the development of treatment/follow-up strategies for ischemia and inflammation related diseases such as stroke and brain edema