TY - JOUR
T1 - Metoclopramide
T2 - A novel and safe immunomodulating agent for restoring the depressed macrophage immune function after hemorrhage
AU - Zellweger, René
AU - Wichmann, Matthias W.
AU - Ayala, Alfred
AU - Chaudry, Irshad H.
PY - 1998/1
Y1 - 1998/1
N2 - Background and Objective: Recent studies have shown that administration of the anterior pituitary hormone, prolactin, after hemorrhage restored the depressed immune responses that are observed under those conditions. Because metoclopramide (MCP) is known to increase prolactin secretion and ultimately plasma prolactin levels, we attempted to determine whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macrophage immune function after severe hemorrhage. Design, Materials and Methods: Mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then adequately resuscitated and segregated into two groups. One group received saline vehicle; animals in the other group were treated with metoclopramide (100 μg/100 g body weight, subcutaneously) before resuscitation. Two hours after saline or MCP injection, the animals were killed and macrophage as well as splenocyte cultures established. Plasma corticosterone levels were also measured. Results: The proliferative capacity of the splenocytes as well as their ability to release interleukin (IL)-2 and IL-3 in response to mitogen was markedly improved in animals that had hemorrhaged and that were treated with MCP 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, treatment with MCP prevented the increase in blood corticosterone levels seen after severe hemorrhage. Conclusion: These results support the concept that the immunosuppression after hemorrhage may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, MCP may be a useful adjuvant in the treatment of the traumahemorrhagic shock-induced immunosuppression.
AB - Background and Objective: Recent studies have shown that administration of the anterior pituitary hormone, prolactin, after hemorrhage restored the depressed immune responses that are observed under those conditions. Because metoclopramide (MCP) is known to increase prolactin secretion and ultimately plasma prolactin levels, we attempted to determine whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macrophage immune function after severe hemorrhage. Design, Materials and Methods: Mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then adequately resuscitated and segregated into two groups. One group received saline vehicle; animals in the other group were treated with metoclopramide (100 μg/100 g body weight, subcutaneously) before resuscitation. Two hours after saline or MCP injection, the animals were killed and macrophage as well as splenocyte cultures established. Plasma corticosterone levels were also measured. Results: The proliferative capacity of the splenocytes as well as their ability to release interleukin (IL)-2 and IL-3 in response to mitogen was markedly improved in animals that had hemorrhaged and that were treated with MCP 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, treatment with MCP prevented the increase in blood corticosterone levels seen after severe hemorrhage. Conclusion: These results support the concept that the immunosuppression after hemorrhage may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, MCP may be a useful adjuvant in the treatment of the traumahemorrhagic shock-induced immunosuppression.
KW - Corticosterone
KW - Hemorrhage resuscitation
KW - IL- 1
KW - IL-2
KW - IL-3
KW - IL-6
KW - Macrophages
KW - Metoclopramide
KW - Splenocyte proliferation
KW - Splenocytes
UR - http://www.scopus.com/inward/record.url?scp=0031905851&partnerID=8YFLogxK
U2 - 10.1097/00005373-199801000-00006
DO - 10.1097/00005373-199801000-00006
M3 - Article
C2 - 9464751
AN - SCOPUS:0031905851
VL - 44
SP - 70
EP - 77
JO - Journal of Trauma - Injury, Infection and Critical Care
JF - Journal of Trauma - Injury, Infection and Critical Care
SN - 1079-6061
IS - 1
ER -