Regulation of interleukin-1 production in murine macrophages and human monocytes by a normal physiological constituent

The in vitro production of large quantities of interleukin-1 (IL-1) in mouse peritoneal exudate macrophages and human peripheral blood monocytes is possible through the use of the proteolytic enzyme pepsin and its zymogen pepsinogen. Equal amounts of IL-1 are generated by pepsin in the absence or presence of polymixin B. The addition of pepsin or pepsinogen had no effect on the proliferation of C3H/HeJ thymocytes to the plant mitogen phytohemagglutinin. Pepsin and pepsinogen are present in significant quantities in immune cells and the plasma. Although little is known concerning the physiological role of pepsin and pepsinogen outside of the gastrointestinal system, it may be proposed that the in vivo production of IL-1 may in part be regulated by the cellular and plasma concentrations of pepsin and pepsinogen.