Interleukin-1 secretion by human alveolar macrophages stimulated with endotoxin is augmented by recombinant immune...

We investigated the role of the macrophage-activating factor gamma interferon (IFN) in the in vitro secretion of interleukin-1 (IL-1) from human alveolar macrophages. Macrophages were obtained from 6 normal volunteers and 5 patients by bronchoalveolar lavage. Macrophages were adhered to a plastic surface and then stimulated to secrete IL-1 with concentrations of endotoxin (LPS) ranging from 1 ng/ml to 10 micrograms/ml. Unstimulated macrophages served as a control. Recombinant gamma IFN was added to LPS-stimulated or unstimulated macrophage cultures in concentrations ranging from 0.25 to 1,000 U/ml. After 24 h of culture, supernatants were removed and IL-1 activity was measured by the thymocyte proliferation assay. Gamma IFN directly induced IL-1 secretion from macrophages of 2 of the subjects. In the presence of LPS, gamma IFN markedly augmented IL-1 secretion from macrophages of 10 of the 11 subjects. Gamma IFN could prime macrophages for increased response to LPS after 1 h of incubation. We conclude that gamma IFN provides a modulating signal for in vitro LPS-induced IL-1 secretion from alveolar macrophages and may enhance macrophage reactivity to inflammatory mediators in vivo.