CYTOKINE GENE-EXPRESSION IN SPLENIC MACROPHAGES AND KUPFFER CELLS FOLLOWING HEMORRHAGE

TNF-alpha, IL-1, IL-6 and TGF-beta are important macrophage-derived me diators which play the pleiotropic role in inflammatory, metabolic, he matopoietic and immunologic processes, Studies have shown that haemorr hagic shock without significant tissue trauma induces profound immunos upression which is associated with elevated plasma levels of TNF-alpha IL-1, IL-6 as well as TGF-beta. Furthermore, Kupffer cells but not th e splenic M phi isolated from post-haemorrhaged animals showed an incr eased capacity to release inflammatory cytokines in response to LPS st imulation in vitro. However, it remains unknown whether the innate (i. e. in the absence of LPS stimulation) cytokine genes expression in Kup ffer cells and splenic M phi is affected by haemorrhage, To determine this, C3H/HeN male mice were bled to and maintained at a mean arterial blood pressure of 35 mmHg for 60 min, and then adequately resuscitate d, Splenic macrophages and Kupffer cells were isolated at 1 h after ha emorrhage, Total RNA was extracted and cytokine mRNA was detected by s emi-quantitative reverse transcription and polymerase chain reaction ( RT-PCR), The results demonstrate that haemorrhage significantly elevat ed the mRNA accumulation of TNF-alpha, IL-1 beta, TGF-beta while IL-6 gene expression in Kupffer cells and splenic M phi was only slightly i ncreased, Since Kupffer cells but not the splenic M phi showed increas ed cytokine release, it could be concluded that the differential regul ation of cytokine release by these two macrophage populations followin g haemorrhage may be due to the divergence of the cytokine at the tran slational level, This difference between splenic M phi and Kupffer cel ls might due to the different cellular composition, anatomical locatio n and physiological environment in which these two fixed tissue macrop hage populations reside.