Effect of lymphokines on the production of cytostatic protein factors from human monocytes.

The effect of activating human monocytes in vitro with lymphokines on the production of cytostatic protein factor(s) (CF) was investigated. Upon exposing the monocytes to either lymphokines or lipopolysaccharide (LPS) the amount of CF released was increased approximately fivefold compared to the amount released from unexposed monocytes. With sequential lymphokine and LPS treatment CF release increased nearly 10-fold. Even 10 min lymphokine activation before LPS exposure enhanced CF production significantly. The enhanced CF production was detected between 5 and 10 hr after lymphokine activation. The RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide reduced the lymphokine-induced CF production in a dose-dependent manner, indicating that lymphokines augment both CF mRNA and CF protein synthesis. When monocytes were exposed to LPS on both Day 2 and Day 4 of culture, the amount of CF obtained on Day 4 was reduced compared to that obtained on Day 2. A significant increase in CF production, however, was observed when the monocytes were activated with lymphokines before the second exposure to LPS on Day 4, supporting the view that lymphokines initiate synthesis of CF in monocytes. Upon ion exchange chromatography, chromatofocusing, and gel filtration the same elution profiles of CF were obtained irrespectively of whether the monocytes had been activated with lymphokines or not. This indicates that lymphokines induce an increased production of the same factor(s) which was obtained in the absence of lymphokines.