Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1

Abstract. Interleukin- 1 (IL- 1) is a mediator released by stimulated mononuclear phagocytes that is thought to play an important role in modulating T and B lymphocyte activation as well as in contributing to the febrile response and other inflammatory processes. Circulating mononuclear phagocytes, blood monocytes, readily release IL- I when stimulated. However, the ability of lung mononuclear phagocytes, alveolar mac-rophages, to dispose of the large daily burden of inhaled antigens without stimulating an inflammatory response suggests that the release of IL-I by alveolar macrophages may differ significantly from that of blood monocytes. To evaluate this hypothesis, normal autologous alveolar macrophages, obtained by bronchoalveolar lavage, were compared with blood monocytes for their ability to release IL-I in response to a standard stimulus, lipo-polysaccharide (LPS). Alveolar macrophages were found to be at least 1,000 times less sensitive to LPS than blood monocytes. Furthermore, alveolar macrophages released significantly less IL-1 than blood monocytes (26±11 vs. 128±21 U / 106 cells * 24 h, respectively, after stimulation with 10,ug/ml of LPS, P < 0.001). This difference was not due to the release of substances by macrophages, which inhibited lymphocyte proliferation in response to IL-1, or to degradation of IL-I by macrophages. Culturing macrophages in the presence of indomethacin and dialysis of macrophage supernatants did not affect the difference, and culturing macrophages with monocytes did not decrease detectable IL-1 activity from the monocytes. The IL-1 produced by the two cel