MELATONIN ADMINISTRATION ATTENUATES DEPRESSED IMMUNE FUNCTIONS AFTER TRAUMA-HEMORRHAGE

The pineal hormone melatonin has been used in clinical trials in patie nts suffering from AIDS and also as an adjuvant for cancer therapy, Al though melatonin has been reported to have beneficial effects in some animal models of immune dysfunction, it remains unknown whether this h ormone has any salutary effects on immunity following soft-tissue trau ma and/or major blood loss. To study this, soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (arterial BP 35 +/- 5 mm Hg) were induced in C3H/HeN mice, The mice were resuscitated after 90 min of hypotension with the shed blood and lactated Ringer's solution. Tr eatment with saline, vehicle, or melatonin (10 mg/kg BW) subcutaneousl y was administered in the evening of the day of surgery and again on t he following evening. All animals were sacrificed at 48 hr following t rauma-hemorrhage and resuscitation to obtain plasma, splenocytes, as w ell as splenic and peritoneal macrophages (M phi). The results indicat e that melatonin administration after trauma-hemorrhage significantly improved the depressed immune functions, as evidenced by the restorati on of M phi IL-1 and IL-6 release, as well as significantly improved s plenocyte IL-2 and IL-3 release and splenocyte proliferative capacity. No differences in circulating corticosterone levels between vehicle- and melatonin-treated animals were observed. This is the first study t o show that melatonin, which is reported to be free of adverse side ef fects, can be considered a safe and effective therapeutic agent for re storing the depressed immunological function after soft-tissue trauma and hemorrhagic shock. (C) 1996 Academic Press, Inc.