Regulation of human natural killing. I. The role of monocytes, interferon, and prostaglandins

We have found that human endogenous natural killer activity as measured in a rapid ⁵¹Cr release assay is unaffected by the presence of monocytes. Moreover, stimulation of natural killer cells by poly I:C is independent of monocytes. In contrast, the presence of monocytes in a mixed population of mononuclear cells that have been stimulated by poly I:C suppresses NK activity. The suppression is shown to be partially reversible if indomethacin (10 ^-6 M) is added to the cultures during stimulation. Culture supernatants of monocytes stimulated with poly I:C are shown to contain PGE ₁ in a radioimmunoassay, and have NK inhibitory activity comparable to that obtained with exogenous PGE ₁ added to NK assays at a concentration range of 10 ^-7 to 10 ^-9 M. Culture supernatants from poly I:C-stimulated monocytes do not have detectable levels of antiviral activity. In contrast, plastic nonadherent cells stimulated with poly I:C produce significant levels of interferon (100 to 200 U/ml/2 x 10 ⁶ cells) but almost undetectable amounts of PGE. Supernatants of nonadherent cells incubated with indomethacin (10 ^-6 M) alone augment NK activity. Taken together, the results suggest that stimulation of mononuclear cells with poly I:C is dependent on and regulated by the relative levels of interferon produced by lymphocytes and PGE produced by monocytes.