Antitumor effect of erythromycin in mice.

Oral administration of erythromycin in the dose range of 1-10 mg/kg increased the survival times of tumor-bearing mice in both allogeneic and syngeneic mouse systems by two- to three-fold as compared with those of vehicle control mice, with the maximum effect at a dose of 5 mg/kg/day. During the early phase of tumor transplantation, tumoricidal macrophages and natural killer cells were active in the antitumor resistance of erythromycin-treated mice. Thereafter, the tumoricidal activity of macrophages became stronger as serum levels of interleukin-4 (IL-4) rose. Furthermore, treatment of mice with anti-IL-4 monoclonal antibody abolished the antitumor resistance conferred by erythromycin. These results indicate that erythromycin exhibits an indirect antineoplastic activity by enhancing the production of IL-4 which augments the tumoricidal activity of macrophages.