Detection of IL-1α and IL-1β in the supernatants of paraformaldehyde-treated human monocytes: Evidence against a membrane form of IL-1

The concept of a membrane form of IL-1 arose from the observation that paraformaldehyde-treated macrophages display IL-1 bioactivity. Thus far, the biochemical characterization of a membrane form of the molecule has not been reported. In a recent publication we demonstrated that murine IL-1α can be detected in the supernatants of paraformaldehyde-treated macrophages. These data indicate that the phenomenon of membrane IL-1 may result from leakage of IL-1 from inadequately fixed cells. In the current report we have extended our studies toward the examination of human IL-1α and IL-1β. IL-1 activity can be detected in the supernatants of paraformaldehyde-treated human monocytes. Although anti-IL-1α, but not anti-IL-1β, antibodies can efficiently block the IL-1 bioactivity, both IL-Iα and IL-1β can be found by immunoprecipitation in the supernatants of the fixed monocytes. IL-1α is efficiently processed to the low m.w. form, whereas IL-1β remains predominantly as the inactive, precursor molecule. IL-1 is not found in the supernatants of monocyte membrane preparations, demonstrating that the leakage of IL-1 is from an intracellular, rather than membrane-bound source.