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 alpha-beta interferon (IFN) on NK activity in normal, cyclophosphamide (CY)-treated, tumor bearing or irradiated and bone marrow reconstituted mice and 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 micrograms/mouse daily X 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.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D002678:Chimera; D003520:Cyclophosphamide / Q000494:pharmacology; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*
D007370:Interferon Type I; D011459:Prostaglandins E, Synthetic; D003520:Cyclophosphamide; D015064:16,16-Dimethylprostaglandin E2