A system establishment compatibility profiles for artificial oxygen carriers and other substances.
Worldwide, great efforts are being made to develop a clinically useful artificial oxygen carrier. Toxicological and immunological compatibility is generally tested using animal experiments but inflammatory parameters in particular show large species-specific differences. Therefore, we developed an in vitro system using human components to establish a compatibility profile of unknown compounds. The test system comprises induction of hemolysis, activation of complement (C3a), induction/suppression of cytokine production, influence on cell proliferation, direct toxicity on peripheral leukocytes, and phagocytosis of the material under test and of microbes. The test system will be described, along with results of various perfluorocarbon emulsions. When testing lecithin-based perfluorodecalin (PFD) emulsions, and comparing them to Pluronic-based PFD emulsions, we could show that Pluronic-based emulsions were virtually untoxic to peripheral human leukocytes. They neither inhibited cell proliferation nor caused any hemolysis, but caused mild to moderate inhibition of endotoxin-induced cytokine production. At the same time, lecithin-based PFD emulsion caused substantial cytotoxicity in phagocytic cells like monocytes (60-100% after 24 h incubation) and granulocytes (10-20% after 24 h incubation). They also suppressed endotoxin-induced cytokine production in monocytes to more than 98% and inhibited cell proliferation of an endothelial (ECV 304) and a monocytic cell line (MonoMac6) to more than 95%.
Institut für Transfusionsmedizin, Tübingen, Germany.
S
S
Dinkelmann
W
W
Röhlke
H
H
Meinert
H
H
Northoff
D001802:Blood Substitutes / Q000494:pharmacology* / Q000592:standards / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005079:Excipients / Q000494:pharmacology / Q000592:standards / Q000633:toxicity; D005466:Fluorocarbons / Q000494:pharmacology* / Q000592:standards / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008422:Materials Testing; D010713:Phosphatidylcholines / Q000494:pharmacology / Q000592:standards / Q000633:toxicity; D020442:Poloxamer / Q000494:pharmacology / Q000592:standards / Q000633:toxicity
D001802:Blood Substitutes; D005079:Excipients; D005466:Fluorocarbons; D015850:Interleukin-6; D010713:Phosphatidylcholines; D020442:Poloxamer; C008805:perfluorodecalin