Melatonin administration has been reported to have beneficial effects on immune function in some clinical studies and in several animal models of immune dysfunction. Furthermore, recent studies suggest beneficial effects of
melatonin on depressed immune function following
trauma-
hemorrhage. Nonetheless, it remains unknown whether this
hormone has any salutary effects on survival following
hemorrhagic shock and subsequent septic challenge. Male C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 +/- 5 mm Hg for 90 min, adequately resuscitated, and 48 hr thereafter subjected to
sepsis (cecal
ligation and
puncture; CLP).
Melatonin-treated mice received either short-term treatment on Days 1 and 2 after
hemorrhage or continuous treatment throughout the study. Treatment with vehicle (10%
ethanol in
normal saline) or
melatonin (10 mg/kg
body weight) was administered daily starting in the evening of the day of
hemorrhage/
sham-operation. Short-term
melatonin administration after
hemorrhage significantly improved survival in animals subjected to septic challenge. Continuous
melatonin treatment did not improve survival, as compared to vehicle-treated mice subjected to
shock and CLP. Moreover, continuous
melatonin treatment in
sham-operated animals significantly increased mortality compared to short-term-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 effects of short-term
melatonin administration in the treatment of immune dysfunction following
hemorrhagic shock.