INVOLVEMENT OF MACROPHAGES IN THE ERADICATION OF ESTABLISHED METASTASES FOLLOWING INTRAVENOUS-INJECTION OF LIPOSOMES CONTAINING MACROPHAGE ACTIVATORS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (2) , 496-501
Abstract
Liposomes containing encapsulated lymphokines or muramyl dipeptide (MDP), when injected i.v. into C57BL/6 mice, produce significant destruction of established lung and lymph node metastases from a s.c. highly metastatic B16-BL6 melanoma. Apparently, eradication of the metastases is mediated by the activation of host macrophages to the tumoricidal state. Results from 3 separate types of experiments support this conclusion; when macrophage-activating agents such as lymphokines or MDP were delivered in liposomes that were not efficiently retained in the lung, little or no activation of lung macrophages was observed and growth of metastases was unaltered; eradication of metastases was not observed when tumor-bearing animals were treated with agents that impaired macrophage function (e.g., silica, carrageenan, hyperchlorinated drinking water) prior to systemic therapy with liposome-encapsulated lymphokines or liposome-encapsulated MDP; macrophages activated in vitro by liposome-encapsulated MDP and then injected i.v. into mice bearing experimental lung metastases also significantly inhibited lung metastases. The augmented host response against pulmonary and lymph node metastases generated by the systemic administration of liposome-encapsulated lymphokines or MDP may be mediated via activated cytotoxic macrophages.