Membrane-associated interleukin 1 activity on human U937 tumor cells: stimulation of PGE2 production by human chondrosarcoma cells.

Membrane-associated interleukin 1 (IL 1) activity was induced on the human macrophage tumor cell line, U937, by pretreatment with phorbol myristic acid (PMA). Incubation of PMA-treated, paraformaldehyde-fixed U937 cells with the murine cell line D10.G4.1 in the presence of concanavalin A caused an increase in DNA synthesis as measured by the uptake of tritiated thymidine. Paraformaldehyde-fixed U937, not pretreated with PMA, showed little or no activity. A rabbit polyclonal antibody directed against human IL 1 neutralized all membrane-associated IL 1-like activity, as measured by the inhibition of D10.G4.1 cell proliferation. PMA-treated U937 caused a pronounced enhancement of PGE2 production from a human chondrosarcoma cell line, SW-1353. Membrane-associated IL 1 induced a more potent PGE2 response than did a maximal concentration of soluble IL 1. Rabbit antihuman IL 1 neutralized membrane-bound IL 1 induction of PGE2. The data presented here raise the possibility that membrane-bound IL 1 may play a primary role in the pathophysiology of the inflammatory disease process.