The effects of augmentation or V₁ blockade of peripherally released AVP during bacterial infection
Creators: name: Korn, Jeanne Ann
Publisher: name: University of British Columbia
Year: 2010

description: Research into the effects of fever has recently had a resurgence of interest with the finding that fever has a definite beneficial role in host defense during bacterial infection in lizards, frogs and fishes. Studies in mammals have not been so definitive. For example, prevention of fever by non-steroidal anti-inflammatory drugs has reduced survival in rabbits but artificially increasing the febrile response in rats has decreased survival. Few studies, however, have sought to determine the important contribution of other physiological variables to the febrile response, focusing rather on simply the rise in temperature. Arginine Vasopressin (AVP) has been shown to be released both centrally and peripherally in high quantities during fever. Release of AVP into the ventral septal area (VSA) of the brain serves as an endogenous antipyretic preventing potentially harmful body temperature increases. The possible role peripherally released AVP plays during infection has not been clearly established, thus these studies were conducted to make a preliminary assessment of that role. Previous experiments have demonstrated that peripherally released AVP may have important functions other than the maintenance of water balance that might contribute to host defense against infection. These include maintenance of cardiovascular function, stimulation of glycogenolysis and gluconeogenesis in the liver, stimulation of phagocytic activity in the reticulo-endothelial system and increases in corticosteroid concentration in the blood. In the experiments reported here, augmentation of the normal AVP response during infection due to gram negative bacteria, altered the thermoregulatory response. There was a pronounced hypothermic phase occurring at 12 hours after injection of 0.5 ml live E. coli bacteria. Additionally, fever at 24 hours was slightly diminished in the AVP infused rats. However, AVP augmentation did not significantly alter the survival of the rats as compared to saline controls. Blockade of endogenously released AVP at the receptor prior to a single injection of live E. coli bacteria, resulted in an increased febrile response. The difference in body temperature from baseline 24 hours after injection was greater in the V₁ antagonist-infused rats. Recovery time was increased in the antagonist-infused rats indicating a possible role of AVP in the acute phase reaction to bacteria. Again, survival did not differ. In the longer term infection model, which involved repeated injections of bacteria, receptor-antagonism did not significantly alter the course of infection as measured by body temperature. There were some differences between the two groups particularly in the first four hours, as the antagonist-infused rats had a pronounced hypothermia, again suggesting some involvement with the acute phase reaction. The data from the long-term infection model suggest that other compensatory mechanisms are able to replace the contribution of AVP acting at the V₁ receptor or that endogenous AVP release is increased to such an extent as to replace the antagonist at the receptor site. A systematic series of experiments combining and eliminating other hormones released during sepsis would be required to determine the possible synergism or redundancy these hormones have during infection. In summary, AVP clearly has some involvement in the cascade of events involved in the defensive reaction to infection, but AVP acting at the V₁ receptor does not play a crucial role in the outcome utilizing this infection model.