HETEROGENEITY OF KUPFFER CELLS AND SPLENIC, ALVEOLAR, AND PERITONEAL-MACROPHAGES FOR THE PRODUCTION OF TNF, IL-1, AND IL-6

Kupffer cells and alveolar, splenic, and peritoneal macrophages from n ormal rats were incubated for various periods of time in the presence of LPS, and the culture supernatants were analyzed for IL-6, IL-1, and TNF. There was very little difference in the amounts of the cytokines produced by the macrophages when stimulated with 0.01-10 mu g/ml of L PS. The shapes of the time course curves for the production of the cyt okines by the different types of macrophages were generally similar, a lthough only Kupffer cells continued to produce IL-6 throughout the en tire incubation period and splenic macrophages showed a lag period in the production of IL-1. Kupffer cells produced more IL-6 than that pro duced by the other populations of macrophages, and alveolar macrophage s produced more IL-1 compared to that produced by splenic cells. Kupff er cells and peritoneal macrophages produced more IL-6 in 24 h than in 6 h of culture, and splenic macrophages produced more IL-1 in 24 comp ared to 6 h of culture. Alveolar macrophages produced more TNF than th at produced by the other populations of cells but only when integrated over the entire incubation period. These results confirm and extend t he observed functional heterogeneity of macrophages obtained from diff erent tissues of the same animal. This study and future studies will l ead to a better understanding of the role of cytokines in the inflamma tory response.