beta-endorphin and Bacterial-Infections

To understand better the pathogenesis of gram-negative infections, we administered a single intravenous injection of Escherichia coli RE-2 endotoxin (4 ng/kg) to five normal volunteers and periodically measured various host-effector molecules in blood. All subjects had a significant (p less than 0.05) increase in temperature (maximum of 1.3 +/- 0.1 degrees C at 4 hours) and white blood cell count (maximum of 7700 +/- 1800 cells per cubic millimeters at 8 hours). Thymocyte costimulatory activity in blood was markedly increased 2 hours after endotoxin administration but returned to baseline at 4 hours. Blood cortisol and beta-endorphin levels paralleled each other, peaking 4 hours after endotoxin (mean increases of 21 +/- 14 micrograms/dl and p less than 0.01; 18.6 +/- 5.9 pg/ml and p less than 0.05, respectively) and returning to baseline at 8 hours. Blood histamine levels did not significantly change at any time point after endotoxin administration. Since thymocyte costimulatory activity was the first of the measured parameters to achieve peak blood levels, we suggest that endotoxin-induced increases in various cytokines may contribute to the increases in the other measured parameters and thereby play a significant role in the pathogenesis of gram-negative infections.

Topics: Adult; Bacterial Infections; beta-Endorphin; Biological Factors; Cell Division; Cells, Cultured; Cytokines; Endotoxins; Escherichia coli; Gram-Negative Bacteria; Histamine; Humans; Hydrocortisone; Injections, Intravenous; Interleukin-2; Leukocyte Count; Thymus Gland; Time Factors

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.

Topics: Adrenal Cortex Hormones; Animals; Bacterial Infections; beta-Endorphin; Blood Glucose; Dogs; Endorphins; Escherichia coli Infections; Female; Gentamicins; Hydrocortisone; Male; Methylprednisolone; Neutrophils; Time Factors

A 0.01 and 0.1-mg/kg dose of iv naloxone was administered to seven patients in septic shock, in order to evaluate naloxone's hemodynamic effect and possible relation to changes in plasma beta-endorphin and catecholamine levels. Naloxone failed to modify cardiac index, blood pressure, heart rate, and systemic vascular resistance. Plasma beta-endorphin, norepinephrine, and epinephrine were elevated but did not change after naloxone administration. These results suggest that beta-endorphin release is a consequence but not a cause of shock, and that the beneficial hemodynamic effects of naloxone in animal studies could be related to species differences or nociceptive stimulations.

Topics: Adult; Aged; Bacterial Infections; beta-Endorphin; Endorphins; Epinephrine; Female; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Norepinephrine; Shock, Septic