CYTOKINE PRODUCTION IN HUMAN AND RAT MACROPHAGES AND DICATECHOL ROOPEROL AND ESTERS

The ability of dicatechol rooperol and esters to inhibit the productio n of cytokines in endotoxin-stimulated human alveolar macrophages, hum an blood monocyte/macrophages, histiocytic cell line U937, and rat alv eolar macrophages was examined in vitro. Rooperol derivatives inhibite d the production of tumour necrosis factor oc, interleukin lp and inte rleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 mu M) than rooperol disulphate (IC50 in the ran ge of 25-75 mu M). The acetate esters also inhibited cytokine producti on in rat alveolar macrophages, whereas the sulphate had little effect . Rooperol and acetate esters, in the same concentration range, decrea sed the production of nitric oxide by rat alveolar macrophages stimula ted by endotoxin. These concentrations of rooperol had no effect on ce ll viability, as indicated by incorporation of C-14-labelled leucine i nto macrophage proteins and their content of lactate dehydrogenase. Th e results obtained suggest that rooperol esters are potentially useful antiinflammatory agents.