In an effort to develop new strategies for immunotherapy of metastatic renal cell carcinoma, we investigated the therapeutic potential of interleukin-4 in a visceral renal tumor using the murine Renca renal adenocarcinoma model. Renca cells were implanted underneath the renal capsule of Balb/c mice to induce a primary tumor that spontaneously metastasized to several organs. Established primary renal tumors 4 to 6 mm. in diameter were treated by intralesional administration of recombinant murine interleukin-4 (IL-4). This treatment caused a marked inhibition of the primary tumor growth but had little effect on the progression of metastases in the liver, mesentery and lungs. Immunohistochemistry studies performed on renal tumor sections showed a macrophage infiltration that became predominant 7 days after IL-4 treatment. CD8+ T cells were also observed at the periphery and within the tumor. These data suggest that IL-4 mediated a potent antitumor effect when administered intralesionally although its effects remained localized with no impact on metastases at distant sites. Interleukin-4 antitumor activity seems to be mediated by recruitment of macrophages and T cells in the tumor.
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