INTERACTION OF PLATELET-ACTIVATING FACTOR WITH INTERFERON-GAMMA IN THE STIMULATION OF INTERLEUKIN-1 PRODUCTION BY HUMAN MONOCYTES

Platelet-activating factor (PAF) produces both early and late inflammatory responses in vivo. The late and persistent responses to PAF may result from the production of cytokines, such as interleukin-1 (IL-1). The effects of PAF on IL-1 release by human monocytes were studied with PAF alone and in combination with interferon-γ. These studies involved the use of D10.G4.1 cells in a proliferation assay to determine the actual concentration of active IL-I in monocyte supernatant and pellet fractions. These studies confirmed that PAF stimulates IL-I release at two different ranges of PAF concentrations, 100 fM to 1 pM and 100 pM to 1 nM. PAF inhibited IL-1 release at 1 or 10 pM. PAF effects on IL-1 release were specific to the form of PAF that is biologically active in most systems; (S)-PAF and lyso-PAF had no effect. When monocytes were incubated with both PAF and interferon-γ, IL-1 release was greatly stimulated at the same two ranges of PAF cncentrations, 100 fM to 1 pM and 100 pM to 1 nM of PAF. PAF and interferon-γ interacted synergistically to enhance significantly the release of IL-1. © 1990 Mosby-Year Book, Inc.