Prolactin inhibits the increased cytokine gene expression in Kupffer cells following haemorrhage.
Kupffer cells are an important source of proinflammatory cytokines and contribute to the systemic inflammatory response observed following haemorrhagic shock. The systemic release of cytokines, such as TNF-alpha, IL-1 beta, IL-6, etc., has been associated with the decreased host immune and organ dysfunction following hypotension. Studies indicate that anterior pituitary hormone prolactin (PRL) plays an important role in the regulation of lymphocyte proliferation and macrophage function in vivo, as well as in vitro. However, it is not known what effects PRL administration has on Kupffer cells proinflammatory mediator release following haemorrhage. Therefore, it was the aim of this study to determine the effect of in vivo PRL administration on cytokine gene expression in Kupffer cells after haemorrhage. To study this, C3H/HeN male mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 60 minutes, then resuscitated with shed blood, and segregated into two groups: one group was treated with PRL (100 micrograms/25 g body weight subcutaneously) while the other group received saline-vehicles. This was followed with lactated Ringer's solution (2 x the volume of shed blood). Two hours thereafter, the animals were sacrificed, Kupffer cells were isolated and stimulated with or without 10 micrograms/ml LPS for 1 hour. Total RNA was extracted and cytokine mRNA was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrated that haemorrhage markedly increased the level of mRNA for IL-1 beta, IL-6, TGF-beta and TNF-beta in Kupffer cells. However, in vivo PRL treatment significantly decreased the cytokine gene expression in Kupffer cells following haemorrhage. This indicates that PRL may be useful in blunting the systemic inflammatory response associated with cell and organ depression following shock.
Zhu
X H
XH
Department of Surgery, Michigan State University East Lansing 48824, USA.
Zellweger
R
R
Ayala
A
A
Chaudry
I H
IH
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006470:Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011388:Prolactin