PROLACTIN - A NOVEL AND SAFE IMMUNOMODULATING HORMONE FOR THE TREATMENT OF IMMUNODEPRESSION FOLLOWING SEVERE HEMORRHAGE

Recent studies have shown that the anterior pituitary hormone prolacti n, together with various cytokines, plays an important role in maintai ning normal immune responses. Although there is evidence that prolacti n may be a significant immunotropic hormone that can counteract the im munosuppressive effects of drugs such as cyclosporine, morphine, or gl ucocorticoids, it remains unknown whether prolactin administration has any salutary effects on the depressed immune responses following seve re hemorrhage. To study this, mice were bled to and maintained at a me an arterial pressure of 35 mm Hg for 60 min, then adequately resuscita ted and segregated into two groups. One group received saline-vehicle (hem-SS); animals in the other group were treated with prolactin (hem- PRL) (100 mu g per 25 g BW, subcutaneously) immediately before resusci tation. Two hours following saline or prolactin injection, splenocytes (SPL) were harvested and assessed for proliferative capacity (PC) and their ability to release IL-2 and IL-3. Supernatant lymphokine levels were determined by bioassay. The proliferative capacity of the spleno cytes, as well as their ability to release IL-2 and IL-3, was signific antly depressed in the vehicle-treated hemorrhaged animals, compared t o shams. Treatment with prolactin restored the depressed splenocyte fu nctions seen after severe hemorrhage. These results support the notion that the immunosuppression following hemorrhage and trauma may be med iated by hormones from the hypothalamic-pituitary-adrenal axis. Furthe rmore, our results suggest that the use of prolactin, which did not pr oduce any adverse hemodynamic effects, represents a novel and safe imm unomodulating hormone for the treatment of immunodepression following severe blood loss. (C) 1996 Academic Press, Inc.