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 prod uction and release of IL-1 from dog peripheral blood lymphocytes (PBLs ) in vitro whereas empty liposomes were observed not to induce IL-1 wh en evaluated with the EL-4/CTLL-1 biological assay. Tumor necrosis fac tor was not induced as measured by the L-929 biological assay. Maximum IL-1 induction occurred at doxorubicin concentrations of 0.3-0.8 mug/ ml. Dog PBLs can be classified as low, moderate and high responders ac cording to their response to doxorubicin induced IL-1 release. Agarose immobilized doxorubicin does not induce IL-1 indicating that internal ization 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.