Zinc Concentration and Survival in Rats Infected with Salmonella Typhimurium.

Abstract

This study was designed to examine the survival value of the redistribution of zinc in bacterially-infected mammals. Two hypotheses were tested. (I) The decline in plasma zinc benefits the infected host; therefore preventing the fall in plasma zinc levels during infection will decrease resistance to infection. (II) The loading of zinc by the tissues (especially the liver), rather than the lowering of plasma zinc levels per se is beneficial to the host. To test the above hypotheses % survival was measured in male rats injected iv with live Salmonella typhimurium (a gram negative, intracellular pathogen) when plasma and tissue zinc levels were manipulated. Alzet pumps implanted ip infused zinc or sodium gluconate (controls) from the onset of infection to 72 hours post-infection. Plasma and tissue zinc were manipulated by infusing (1) 180 ug Zn/hr to achieve supranormal plasma and tissue zinc concentrations, (2) 120 ug Zn/hr to prevent the infection induced fall and maintain plasma zinc levels at non-infection levels while raising tissue levels above that of infected controls, and (3) 30 ug Zn/hr to increase tissue zinc levels while allowing the infection induced decrease in plasma zinc. Preventing the fall in plasma zinc during infection enhanced rather than reduced % survival and raising plasma zinc to supranormal levels returned survival to control levels. Loading the liver with an excess of zinc without changing plasma zinc (30 ug Zn/hr) did not increase % survival in the infected host. Loading the tissues with more zinc than seen with infusion of 30 ug Zn/hr enhanced survival if plasma zinc was maintained at non-infection levels (120 ug Zn/hr) but did not enhance survival if plasma zinc was raised to supranormal levels (180 ug Zn/hr). Pretreatment or administration of zinc at the time of infection led to increased % survival compared to administration of zinc 4 hours after the onset of infection. In addition, an inverse relationship was found between the dose of zinc infused and the febrile temperature measured at 4, 8 and 24 hours post-infection although the scatter around the linear relationship was large.