Effect of in vivo administration of prostaglandins and interferon on natural killer activity and on B-16 melanoma growth in mice

We investigated the effect on in vivo administration of 16,16-dimethyl-prostaglandin E₂ (di-M-PGE₂) alone and in combined treatment with α-β interferon (IFN) on (a) NK activity in normal, cyclophosphamide (CY)-treated, tumor bearing or irradiated and bone marrow reconstituted mice and (b) on B-16 melanoma growth. Normal mice inoculated with IFN (30,000 U/mouse, 24 hr before testing) showed a significant increase in NK activity, while those treated with di-M-PGE₂ (10 μg/mouse daily × 4 days) showed a suppressed NK response. No difference was observed between mice treated with di-M-PGE₂ alone and those treated with di-M-PGE₂ associated with IFN. In immunosuppressed animals single treatments were slightly (di-M-PGE₂) or not (IFN) effective, while the combined administration of di-M-PGE₂ and IFN caused a marked increase in NK activity. Moreover, di-M-PGE₂ was able to accelerate the recovery rate of NK activity in bone marrow-reconstituted murine chimeras, suggesting that the synergistic effect of prostaglandins and IFN could derive from the action of di-M-PGE₂ on progenitor pre-NK cells and of IFN on effector cells. Finally, we observed a good correlation between the enhancement of the NK activity and the tumor growth inhibition.