In situ activation of mouse lung macrophages by coadministration of liposomes containing the lipopeptide CGP 31362 and interleukin 2 involves interaction with T lymphocytes and natural killer cells

These studies were undertaken to determine the mechanism for augmented tumoricidal activity of alveolar macrophages (AM) in mice injected intravenously with multilamellar liposomes containing a lipopeptide analogue of Gram-negative bacteria cell wall (MLV-CGP 31362) and intraperitoneally with interleukin 2 (IL-2). BALB/c mice were injected into the kidney with syngeneic renal carcinoma cells. Ten days later, this kidney was resected, and the mice were treated intravenously with MLV-CGP 31362 and/or intraperitoneally with IL-2. Treatment with MLV-CGP 31362 led to a reduction in the number of lung metastases, whereas treatment with IL-2 alone did not. The coadministration of intravenous liposomes and intraperitoneal IL-2 produced significant eradication of lung metastases. MLV-CGP 31362 (iv) and IL-2 (ip) were injected both into control immune-competent and nude mice or into mice whose natural killer (NK) cells had been depleted by systemic administration of anti-asialo GM₁ antibodies. MLV-CGP 31362 activated tumoricidal properties in AM of all groups of mice. The additive tumoricidal activation of AM by IL-2 was associated with its effects on both T cells and NK cells.