PROLACTIN INHIBITS THE INCREASED CYTOKINE GENE-EXPRESSION IN KUPFFER CELLS FOLLOWING HEMORRHAGE

Kupffer cells are an important source of proinflammatory cytokines and contribute to the systemic inflammatory response observed following h aemorrhagic shock, The systemic release of cytokines, such as TNF-alph a, IL-1 beta, IL-6, etc., has been associated with the decreased host immune and organ dysfunction following hypotension, Studies indicate t hat 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 P RL administration has on Kupffer cells proinflammatory mediator releas e following haemorrhage, Therefore, it was the aim of this study to de termine the effect of in vivo PRL administration on cytokine gene expr ession in Kupffer cells after haemorrhage, To study this, C3H/HeN male mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then resuscitated with shed blood, and segregated i nto two groups: one group was treated with PRL (100 mu g/25 g body wei ght subcutaneously) while the other group received saline-vehicles. Th is was followed with lactated Ringer's solution (2 x the volume of she d blood). Two hours thereafter, the animals were sacrificed, Kupffer c ells were isolated and stimulated with or without 10 mu g/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 leve l 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 g ene expression in Kupffer cells following haemorrhage, This indicates that PRL may be useful in blunting the systemic inflammatory response associated,vith cell and organ depression following shock. (C) 1996 Ac ademic Press Limited