Corticosteroid alteration of human monocyte to macrophage differentiation

Human monocyte to macrophage differentiation in vitro is associated morphologically with an increased cell size, an increased number of lysosomes, and rough endoplasmic reticulum. Functional changes associated with monocyte to macrophage differentiation include increased tumoricidal activity and increased cell protein, acid phosphatase, and 5'-nucleotidase. Hydrocortisone succinate (HCS) at 2.5 microM markedly altered monocyte to macrophage differentiation: HCS inhibited the development of tumoricidal activity and the increased levels of cell protein, acid phosphatase, and 5'-nucleotidase. By transmission electron microscopy, macrophages incubated with HCS failed to develop an increased complement of lysosomes and developed an increased number of membrane-bound electron lucent vacuoles. Dexamethasone inhibited the development of tumoricidal activity at a 10-fold lower concentration than HCS. HCS also markedly inhibited monocyte 3H-uridine incorporation. Mechanisms of HCS alteration of monocyte differentiation are discussed. These data suggest that corticosteroid alteration of monocyte differentiation may be a mechanism of HCS immunosuppression in vivo.