Unlike NAC, ambroxol is able to not only inhibit acute mediator release from mast cells and leukocytes but also reduce immunomodulatory cytokine generation from basophils and may have beneficial effects in the treatment of allergic respiratory diseases.

The effect of intravenous administration of the glucocorticoid prednylidene on the macrophage subtype RM 3/1 in the peripheral blood of man was studied. Injection of 60 mg steroid resulted in an increase in the proportion of RM 3/1 positive monocytes 12 h after application from the basic level to about 80%. After 24 h the number of RM 3/1 positive cells decreased but remained elevated over the basis rate for a period of at least 15 days. Similar results were obtained after administration of 30 or 6 mg prednylidene even if the peak value occurred with a delay of 12 h after 6 mg. A dose- and time-dependent induction of the RM 3/1 positive subtype could also be demonstrated in vitro by the addition of prednylidene or dexamethasone to cultured purified human monocytes/macrophages. Deoxycortone or indomethacin had no effects. These results suggest that glucocorticoids exert their influence on cells of the mononuclear phagocytic lineage by inducing a distinct monocyte/macrophage subpopulation which seems to be associated with anti-inflammatory functions.

Some recent observations have indicated that cells other than mast cells, notably macrophages, may contain significant amounts of histamine. Using a histamine-specific radioimmunoassay, we found that human blood monocytes and lymphocytes contain about 0.05 pg histamine/cell. Various other cells, e.g. fibroblasts, colorectal tumor, kidney and ovarian cells, and murine bone marrow derived macrophages contained markedly less histamine (< 0.008 pg/cell). Ionophore A23187 (1 microM) released up to 50% of the total histamine from monocytes and lymphocytes. C5a caused a dose-dependent histamine release of up to 40% in monocytes and up to 20% in lymphocytes. Substance P induced a release only in cells of certain donors. Lipopolysaccharide, concanavalin A, and compound 48/80 had no effect. Culturing of the cells caused a loss of cellular histamine and its releasability. In view of the huge numbers of monocytes and lymphocytes in the blood, the histamine in these cells has to be taken into account under both physiological and pathophysiological conditions.

Glucocorticoids exert their anti-inflammatory activity by modulating the functions of various cell types including macrophages. They also induce the generation of a distinct macrophage subtype defined by the surface antigen RM3/1 which appears to be associated with the down-regulation of inflammation. Supernatants from these cells were found to exert a dose-dependent anti-inflammatory effect, particularly in the early phase as shown in the 5-hydroxytryptamine (5-HT) induced footpad edema of mice. By using conventional purification methods the anti-inflammatory factor was found to have a molecular mass of about 78 kD and an isoelectric point of about 7.9. Heat lability and sensitivity to trypsin and proteinase K indicate the protein nature of the anti-inflammatory factor. The inhibition of the early phase of inflammation and the molecular weight suggest that the anti-inflammatory agent released from RM3/1 macrophages is a novel protein different from other anti-inflammatory proteins described so far.