In vivo initiation of unstimulated in vitro interleukin-1 release by alveolar macrophages

Alveolar macrophages (AM) can be stimulated in vitro with material such as lipopolysaccharide, and this activation releases cytokines, collectively called interleukin-1, that can stimulate local cells such as fibroblasts, systemic cells such as lymphocytes, and/or distant parenchymal cells such as hepatocytes. During murine infection with the nematode Nippostrongylus brasiliensis, AM are activated as the parasite larvae migrate through the lung. We examined AM for unstimulated release of lymphocyte-activating factor (LAF) and hepatocyte-stimulating factor (HSF) as evidence of in vivo activation. Two days after infection, marked unstimulated release of LAF was demonstrated along with a smaller increase in unstimulated release of HSF activity. Release of both activities could be further augmented by in vitro stimulation with lipopolysaccharide. Eight days after infection unstimulated HSF activity was even higher than on Day 2, whereas unstimulated LAF release retunred to normal. These findings suggest that a natural infective process causes activation of the resident AM population, resulting in release of potent immune and inflammatory-modulating cytokines in situ and that AM play a crucial role in the initiation of host defense and repair responses to infection.