Central administration of IL‐1 receptor antagonist increases vasopressin secretion in late phase of sepsis in rats (876.7)

Abstract

Clinical and experimental studies have reported that the initial phase of sepsis is characterized by elevated plasma vasopressin (AVP) concentrations. However, in the late phase, despite of the significant decrease in the arterial pressure, the AVP secretion decrease and the plasma concentrations remain unusually low, contributing to the hypotension, vasodilator shock, and death. Considering the role of AVP in the vasopressor response, the elucidation of the mechanisms of this deficient hormone secretion may contribute to therapy during sepsis.The aim of this study was to analyze the effect of IL‐1ra (an Interleukin‐1 receptor antagonist) on sepsis‐induced alterations in plasma AVP and NO, and cerebrospinal fluid (CSF) NO levels. After Wistar rats were intracerebroventricullary injected with 2 ul of IL‐1ra (9 nmol/ or vehicle (PBS 0.01M) sepsis was induced by cecal ligation and puncture (CLP). Blood samples were collected from different groups of rats (n=6‐8/group) by decapitation after 4‐, 6‐ and 24‐h. Specific ELISA and Chemiluminescence assays were used for measurement of AVP and NO concentrations, respectively. All experiments were carried out according to an institutional ethical committee approved protocol.IL‐1ra administration did not alter plasma vasopressin after 4‐ and 6‐h as compared to vehicle in CLP animals. In contrast, after 24‐h AVP levels were significantly (P<0.01) higher in IL‐1ra treated animals as compared to vehicle treated animals. IL‐1ra administration significantly (P<0.01) decreased NO concentration in CSF but not in plasma. Moreover, the survival rate of IL‐1ra treated rats increased by 38% in comparison to vehicle administered animals.In conclusion, the central administration of IL‐1ra increases AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL‐1ra is through reduction of NO concentration in CSF of the septic rats.