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J.Jpn. Surg. Soc.. 81(5): 365-380, 1980
Original article
CLINICAL AND EXPERIMENTAL STUDY OF IMMUNOLOGICAL MECHANISMS IN SEPSIS AND SEPTIC SHOCK
From the analysis of blood samples of 86 surgical patients associated with severe infection and/or shock, following results were obtained.
1) Mean serum level of hemolytic complement activity (CH50) of endotoxin (Et) positive samples (N=32) was significantly lower than that of Et negative samples (N=54).
2) O-antibody titers of these samples against E.coli 0111: B4, 055: B5, 026: B6 and 0127: B8 were not significant clinically.
3) Eleven of 15 patients who were subjected to direct cholangiography (percutaneous or per- T-tube), developed endotoxemia immediately after the contrast medium injection. Five of these who had been suffered from long term biliary infection showed severe clinical shock symptomes with profound drop of serum CH50.
Further experiments were carried out in order to clarify the pathophysiological role of O-antibody and complement in endotoxemia. Results were as followed.
1) In vitro: 1. Certain serial concentrations of Et mixed in specific O-antiserum did not make the gelation of Limulus lysate. 2. Twenty four hours survival rate of lead acetate treated rats which were injected Et incubated with specific O-antiserum of rabbits was significantly better than the groups challanged with Et incubated with control serum or different serotype O-antiserum.
2) In vivo: 1. In Et challanged rabbits, temporary but significant drop of arterial pressure in early stage (initial reaction) was accompanied with profound decrease of serum CH50 level. This was exaggerated as gaining in Et quantity and by preceding immunization with specific O-antigen. 2. Either hydrocortisone or indomethacin pretreatment increased the survival rate of Et challanged rabbits significantly and especially the latter agent suppressed initial reaction completely, but these agents made little influence to the change in CH50 level.
Conclusion: 1) Complement activation by Et which is widely accepted as a defence mechanism in the organism challanged by bacterial toxins, is otherwise a trigger of shock symptomes. 2) While O-antibody enhances complement activation and initial reaction in Et challanged animal, it detoxifies the lethal activity of Et in vitro and suppresses the biological activity of Et on Limulus lysate gelation. 3) Although pretreatment with hydrocortisone or indomethacin rescues the Et challanged rabbits, either agent does not significantly suppress the complement activation by Et. This suggests that Et has some other lethal toxicity than complement activation as well.
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