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.