The pineal
hormone melatonin has been used in clinical trials in patients suffering from
AIDS and also as an adjuvant for
cancer therapy. Although
melatonin has been reported to have beneficial effects in some animal models of immune dysfunction, it remains unknown whether this
hormone has any salutary effects on immunity following soft-tissue
trauma 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. Treatment with saline, vehicle, or
melatonin (10 mg/kg BW) subcutaneously was administered in the evening of the day of surgery and again on the following evening. All animals were sacrificed at 48 hr following
trauma-
hemorrhage and
resuscitation to obtain plasma, splenocytes, as well as splenic and peritoneal macrophages (Mphi). The results indicate that
melatonin administration after
trauma-
hemorrhage significantly improved the depressed immune functions, as evidenced by the restoration of Mphi
IL-1 and
IL-6 release, as well as significantly improved splenocyte
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 to show that
melatonin, which is reported to be free of adverse side effects, can be considered a safe and effective therapeutic agent for restoring the depressed immunological function after soft-tissue
trauma and
hemorrhagic shock.