Induction of dog IL-1 by free and liposomal encapsulated doxorubicin.
Liposomal encapsulated doxorubicin, free doxorubicin and a mixture of free doxorubicin plus empty liposomes were observed to induce the production and release of IL-1 from dog peripheral blood lymphocytes (PBLs) in vitro whereas empty liposomes were observed not to induce IL-1 when evaluated with the EL-4/CTLL-1 biological assay. Tumor necrosis factor was not induced as measured by the L-929 biological assay. Maximum IL-1 induction occurred at doxorubicin concentrations of 0.3-0.8 microgram/ml. Dog PBLs can be classified as low, moderate and high responders according to their response to doxorubicin induced IL-1 release. Agarose immobilized doxorubicin does not induce IL-1 indicating that internalization of doxorubicin is required for IL-1 release. Limulus amebocyte lysate testing of doxorubicin indicates that endotoxin contamination is not responsible for this observed release of IL-1.
Klaich
G M
GM
James T Grace Jr Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
Kanter
P M
PM
D000818:Animals; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D004337:Drug Carriers; D004731:Endotoxins / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D007376:Interleukin-2 / Q000096:biosynthesis*; D008081:Liposomes; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D012685:Sepharose
D004337:Drug Carriers; D004731:Endotoxins; D007376:Interleukin-2; D008081:Liposomes; D004317:Doxorubicin; D012685:Sepharose