The effect of inhibitors of prostaglandin E2 (PGE2) synthesis on monocyte as well as lymphocyte antibody-dependent cellular cytotoxicity (ADCC) against human red blood cells was studied. Effector cells were obtained from normal healthy controls and from patients with previously resected malignant melanoma who were receiving adjuvant immunotherapy with subcutaneous Corynebacterium parvum. Patient monocyte ADCC was significantly increased compared to controls (25% vs 8%) at effector-to-target ratios of 1:2; lymphocyte ADCC was similar in both groups. Indomethacin at 10-6 M significantly augmented monocyte ADCC in patients, but not in controls; lymphocyte ADCC was not affected. Rabbit antibody to human PGE2 had a similar effect on patient monocyte ADCC, suggesting that the mechanism of augmentation was via blocking of PGE2 secreted during the course of the reaction. The data suggest that PGE2 acts as a feedback mechanism to limit monocyte and not lymphocyte ADCC. Furthermore, monocytes must be preactivated for augmentation by PGE2 inhibitors to occur.
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