METOCLOPRAMIDE - A NOVEL AND SAFE IMMUNOMODULATING AGENT FOR RESTORING THE DEPRESSED MACROPHAGE IMMUNE FUNCTION AFTER HEMORRHAGE

Background and Objective: Recent studies have shown that administratio n of the anterior pituitary hormone, prolactin, after hemorrhage resto red the depressed immune responses that are observed under those condi tions, Because metoclopramide (MCP) is known to increase prolactin sec retion and ultimately plasma prolactin levels, we attempted to determi ne whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macr ophage immune function after severe hemorrhage, Design, Materials and Methods: Mice mere bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then adequately resuscitated and segregate d into two groups, One group received saline vehicle; animals in the o ther group were treated with metoclopramide (100 mu g/100 g body weigh t, subcutaneously) before resuscitation, Two hours after saline or MCP injection, the animals were killed and macrophage as well as splenocy te cultures established, Plasma corticosterone levels mere also measur ed. Results: The proliferative capacity of the splenocytes as well as their ability to release interleukin (IL)-2 and IL-3 in response to mi togen was markedly improved in animals that had hemorrhaged and that w ere treated with II ICP compared with saline-injected mice, Moreover, the depressed splenic and peritoneal macrophage IL-1 and IL-6 release after hemorrhage was restored with MCP treatment. Furthermore, treatme nt with MCP prevented the increase in blood corticosterone levels seen after severe hemorrhage. Conclusion: These results support the concep t that the immunosuppression after hemorrhage may be mediated by hormo nes from the hypothalamic-pituitary-adrenal axis. Furthermore, MCP may be a useful adjuvant in the treatment of the trauma-hemorrhagic shock -induced immunosuppression.