Generation of Anti-inflammatory Protein in Glucocorticoid-lnduced Human RM3/1 Macrophages

Abstract

The anti-inflammatory activities of glucocorticoids are supposed to be based on two distinct mechanisms: 1. the downregulation of mediator synthesis, e.g. of the cytokines Il-1, Il-2 Il-4, Il-6, Il-8, tumor necrosis factor-α granulocyte-macrophage colony-stimulating factor and interferon-γ [1,2]; 2. the production of anti-inflammatory proteins, e.g. the lipocortins and vasocortins [3]. Stimulation of peripheral monocytes with glucocorticoid (prednylidene) is followed by the generation of a macrophage subtype which is defined by the expression of the surface antigen RM3/1. In vivo this subtype is associated with the down regulation of the inflammatory process [4,5]. In vitro these cells secrete anti-inflammatory activity.The increasing proportion of RM3/1

macrophages during the first 12–24 h in the presence of prednylidene in culture medium [5] was accompanied by the some proinflammatory activity followed by anti-inflammatory activity from 10 h onwards (Fig.1). The formation of this activity continued when the glucocorticoid was removed from the medium after 40 h. The anti-inflammatory activity showed a dose dependency as is demonstrated in Fig. 2. In this experiment the doses of the protein extract corresponded to the number of macrophages which had produced them (cell equivalents). To make the unitage of the protein extracts independent of varying functions of the cells the anti-inflammatory activity was rather related to the effect of dexamethasone (dexa equivalents).