Differentially increased IL-6 mRNA expression in liver and spleen following injection of liposome-encapsulated haemoglobin.
Injection of the red cell substitute liposome-encapsulated haemoglobin (LEH) induces increased serum interleukin (IL)-6 in the absence of other inflammatory cytokines. In vitro studies found that IL-6 mRNA was increased in Mphi and endothelial cell lines by co-culture with LEH. In the present study, cytokine mRNA expression in extracts of livers, spleens, lungs and kidneys after LEH injection was determined by semi-quantitative RT-PCR. The distribution of cells expressing IL-6 mRNA in livers and spleens was visualized by in situ hydridization; extracts of kidney and lung did not show increased IL-6 mRNA and were not studied further. IL-6 mRNA accumulation in livers and spleens was increased at 4 h following LEH injection and had declined by 24 h. In the liver, cells expressing IL-6 mRNA were located in endothelia of hepatic and portal veins, and hepatic sinuses, Kupffer cells and epithelial cells of bile ducts. Endothelium of hepatic arteries did not express IL-6 mRNA. Lymphocytes, haematopoietic cells and macrophages expressed IL-6 mRNA in spleens. The data suggest that cells of the reticuloendothelial system (RES) might be a significant source of increased plasma IL-6 in vivo after LEH administration.