Abstract
The cellular site(s) and the mechanism(s) of endotoxin-mediated modification of the infectious process in the host were explored by the use of a virulent <i>K. pneumoniae </i>(KPC) infection in mice. The mean survival time of mice increased severalfold after as little as 0.01 μ<i>g </i>endotoxin <i>(S. enteritidis </i>LT<sub>2</sub>), reached a maximum with 1 μg<i>, </i>and actually decreased when 10 μg endotoxin was given intravenously 24 h prior to challenge with KPC. Following 1 μgendotoxin, resistance to infection was quickly established ( < 6 h), reached a maximum between 12–24 h, and was back to normal by 3 days. Albeit less effectively than in intact animals, endotoxin (1 μgi.v. 24 h before challenge) produced a severalfold increase in the survival time after KPC infection in splenectomized mice. At the time of challenge with KPC, there was no hepatomegaly; but the carbon clearance rates (K values) were increased. Administration of thorotrast 2 h prior to infectious challenge completely abolished the antiinfectious effect of the toxin. Under similar conditions, zymosan did not decrease the effect of pretreatment with endotoxin and, if used preventively, actually protracted the survival time of KPC-infected mice. Although repeated intraperitoneal injections of endotoxin increased the liver mass in all cases, they effected only limited increase in resistance to KPC infection in intact, sham-operated, or splenectomized mice. These various properties of endotoxin could be dissociated by the use of actinomycin-D, which completely abolished the development of tolerance to endotoxin, and the activation of the reticuloendothelial system (hepatosplenomegaly, K values) associated with it; but the antibiotic influenced only minimally the endotoxin-mediated increase in resistance to infection with KPC. These studies are discussed with respect to the whole array of host responses elicited by endotoxin.
Published Version
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