Response of humans to gamma-irradiated reference Escherichia coli endotoxin

This study assesses the effect of gamma-irradiation of endotoxin given intravenously to healthy human volunteers. The national reference standard endotoxin derived from E. coli was placed in aqueous medium in sterile-sealed ampoules and divided into four groups. One group received endotoxin with no radiation while the other three received endotoxin with gamma-irradiation at doses of 0.18, 0.36, or 1.08 Mrad. These doses of radiation cause characteristic alterations to the endotoxin molecule, primarily to the O-polysaccharide moiety. Each of the four different preparations of endotoxin was given intravenously to four volunteers at a concentration of 4 ng/kg. The responses for clinical symptoms, cortisol, and growth hormone were significantly and progressively reduced by increasing the irradiation to the endotoxin. Most strikingly, no clinical symptoms were noted with the endotoxin exposed to the highest dose of radiation (1.08 Mrad). Fever, vital signs, white blood cell count, and differential exhibited no statistically significant differences among the groups, but the kinetics of change were altered by increasing doses of gamma-irradiation. Irradiated endotoxin was significantly more effective in decreasing the platelet count than untreated endotoxin. The fever index correlated significantly with maximum temperature, change in temperature, white blood cell count index, mature neutrophil count index, and the cortisol index. Thus, there is dissociation of biological activities for endotoxin in humans due to molecular changes primarily in the O-polysaccharide moiety from exposure to gamma-irradiation.