Enhanced sensitivity to endotoxin induced by the RE stimulant, glucan.
Pretreatment of rats with the RES stimulant, glucan, markedly increases their sensitivity to endotoxic shock. Intravenous administration of S. enteritidis endotoxin (10 micrograms/100 gm B.W.) produced a more severe shock in glucan-pretreated rats than IV injection of 1 mg/100 gm B.W. 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 RE-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, however, was abolished at two hours 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. Thus, 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.
D000818:Animals; D004731:Endotoxins / Q000276:immunology / Q000633:toxicity*; D005936:Glucans / Q000276:immunology*; D008099:Liver / Q000648:ultrastructure; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects*; D011292:Premedication; D051381:Rats; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D013268:Stimulation, Chemical
D004731:Endotoxins; D005936:Glucans; D008775:Methylprednisolone