No abstract

Sepsis has been associated with specific plasma amino acid patterns. Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure. Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated. These changes were more pronounced in severe sepsis. Organ failure was not associated with significantly altered amino acid profiles. No differences were found between sepsis and stress without signs of sepsis. In addition, imminent death was not associated with aberrant amino acid profiles. We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity.

No abstract

Although lipopolysaccharide is capable of directly inducing endothelial permeability, blood-borne tumor necrosis factor-alpha and interleukin-1beta mediate lipopolysaccharide-induced endothelial permeability at low endotoxin concentrations. These findings support the idea that multifactorial inhibition of inflammatory mediators may improve survival in septic patients.

TNF plays a central role in septic shock induced by endotoxin or Gram-negative bacteria. Zymosan can elicit a septic shock-like syndrome in rodents in the absence of endotoxin. TNF and IL-6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL-6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan-induced mortality from 63 to 11.6%, while maximal IL-6 levels were lowered by about 40%. Mechanisms triggering zymosan-induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty-nine per cent of TNF release by macrophages appeared to be triggered by zymosan-bound activated complement. Maximal TNF release also required the presence of natural antibodies against zymosan and zymosan-activated serum. In contrast, maximal IL-6 release was reached upon stimulation with zymosan-activated serum only, while the presence of zymosan particles lowered this response. We conclude that TNF is a crucial mediator in zymosan-induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL-6 release during septic shock is partly dependent on TNF, in vitro trigger mechanisms for IL-6 and TNF differ remarkably.