MELATONIN ADMINISTRATION FOLLOWING HEMORRHAGIC-SHOCK DECREASES MORTALITY FROM SUBSEQUENT SEPTIC CHALLENGE

Melatonin administration has been reported to have beneficial effects on immune function in some clinical studies and in several animal mode ls of immune dysfunction. Furthermore, recent studies suggest benefici al effects of melatonin on depressed immune function following trauma- hemorrhage. Nonetheless, it remains unknown whether this hormone has a ny salutary effects on survival following hemorrhagic shock and subseq uent septic challenge. Male C3H/HeN mice were bled to and maintained a t a mean arterial blood pressure of 35 +/- 5 mm Hg for 90 min, adequat ely resuscitated, and 48 hr thereafter subjected to sepsis (cecal liga tion and puncture; CLP). Melatonin-treated mice received either short- term treatment on Days 1 and 2 after hemorrhage or continuous treatmen t throughout the study. Treatment with vehicle (10% ethanol in normal saline) or melatonin (10 mg/kg body weight) was administered daily sta rting in the evening of the day of hemorrhage/sham-operation. Short-te rm melatonin administration after hemorrhage significantly improved su rvival in animals subjected to septic challenge. Continuous melatonin treatment did not improve survival, as compared to vehicle-treated mic e subjected to shock and CLP. Moreover, continuous melatonin treatment in sham-operated animals significantly increased mortality compared t o shortterm-treated and vehicle-treated animals. While the mechanisms of the differential effects of melatonin administration are yet to be clearly defined, this study, nonetheless, demonstrates the salutary ef fects of short-term melatonin administration in the treatment of immun e dysfunction following hemorrhagic shock. (C) 1996 Academic Press, In c.