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.
Zhu
X L
XL
Henry M. Jackson Foundation, 1401 Rockville Pike, Rockville, MD, 20852, USA.
Pacheco
N D
ND
Dick
E J
EJ
Rollwagen
F M
FM
D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000187:drug effects; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004337:Drug Carriers; D006454:Hemoglobins; D015850:Interleukin-6; D008081:Liposomes; D012333:RNA, Messenger