ENHANCED SENSITIVITY TO ENDOTOXIN INDUCED BY THE RE STIMULANT, GLUCAN

  • 1 January 1980
    • journal article
    • research article
    • Vol. 7  (3) , 225-238
Abstract
Pretreatment of rats with the RES stimulant, glucan, markedly increases their sensitivity to endotoxic shock. I.v. administration of Salmonella enteritidis endotoxin (10 .mu.g/100 g body weight) produced a more severe shock in glucan-pretreated rats than i.v. injection of 1 mg/100 g body weight of endotoxin in normal rats. Endotoxic shock in glucan-sensitized rats was associated with a precipitous increase in serum activity of lysosomal enzymes and a more severe hypoglycemic response. The shocked glucan-pretreated rats died before marked increases in plasma hepatocyte enzyme activity were apparent. Assessment of RES-phagocytic function with the 131I RE test-lipid emulsion revealed a rapid clearance and hepatic uptake of the emulsion in nonshocked glucan-control animals. This hyperphagocytic function was abolished at 2 h after injection of endotoxin. Hepatic ultrastructure in shocked glucan and normal rats revealed extensive sinusoidal changes. Hepatocytes, with the exception of a depletion of glycogen granules, were comparatively intact in the shocked-glucan group as opposed to the shocked control group. Pretreatment with methylprednisolone (60 mg/kg) protected the glucan-treated rats from endotoxin and was relatively more effective in diminishing the hypoglycemic response than preventing a loss of lysosomal integrity. Despite the absence of overt ultrastructural changes in hepatocytes, altered glucoregulation appears to be a significant factor in the enhanced sensitivity of glucan-pretreated rats to endotoxin.