Production of cytokines and PGE₂ and cytotoxicity of stimulated bone marrow macrophages after thermal injury and cytotoxicity of stimulated U-937 macrophages

Bone marrow-derived macrophages from normal and burned rats were cultured for one and four days in the presence of LPS, PHA, or opsonized zymosan as activators, and the supernatants were assayed for the inflammatory mediators TNF, IL-6, and PGE2 and the cells assayed for cytotoxicity. The macrophages responded differently to the various stimuli regarding cytotoxicity and the production of mediators, perhaps implicating the complement receptor CR1 in TNF production and the LPS receptor CD14 or the PHA lectin receptor in IL-6 and PGE2 production and for cytotoxicity. The response of the cells also depended on culture time and postburn time; in addition, macrophages from burned and unburned animals responded differently, depending on postburn day and the type of stimulus. TNF production was generally higher for one-day compared to four-day cultures (i.e., TNF was disappearing in the cultures), but IL-6 and PGE2 production was greater in four-day cultures. The results of this study suggest that thermal injury can contribute to the development of inflammatory and cytotoxic macrophages from bone marrow progenitor cells.