MECHANISMS OF CORTICOSTEROID ACTION ON LYMPHOCYTE SUB-POPULATIONS .3. DIFFERENTIAL EFFECTS OF DEXAMETHASONE ADMINISTRATION ON SUB-POPULATIONS OF EFFECTOR CELLS MEDIATING CELLULAR CYTOTOXICITY IN MAN

  • 1 January 1978
    • journal article
    • research article
    • Vol. 31  (1) , 116-125
Abstract
The effect of dexamethasone (DEX) administration on different populations of mononuclear cells and neutrophils mediating antibody-dependent cellular cytotoxicity (ADCC) against different target cells was investigated. Mononuclear cells (lymphocytes and monocytes) and neutrophils were obtained from 27 normal volunteers at 0, 4, 24 and 48 h after oral administration of 21 mg of DEX. ADCC was determined utilizing the following targets: human red blood cells (HRBC), [human] Chang liver cells (Ch) and human heart cells (HHC). The predominant mononuclear effector in HRBC killing was a monocyte and in Ch and HHC killing, a K [antibody dependent killer cell] cell. DEX produced a profound monocytopenia and lymphocytopenia at 4 h with a return of lymphocyte counts to normal and monocyte counts to supra-normal at 24 h. At the point of maximal monocytopenia, monocyte-mediated HRBC killing decreased from a geometric mean of 14 to 4 lytic units/108 effector cells (P < 0.05) and rebounded at 24 h to a mean of 39 lytic units (P < 0.02) with the rebound monocytosis. At the point of absolute lymphopenia (4 h), there was a relative enrichment in the proportion of lymphocytes bearing an Fc receptor (K cells, P < 0.01). Concomitant with this was an increase in ADCC against Ch and HHC from geometric means of 1121 to 7172 lytic units and 939 to 7354 lytic units (P < 0.001), respectively. A major action of DEX administration on mononuclear ADCC was to enrich differentially or deplete different effector cells to and from the circulation, causing changes in cytotoxicity. Since the cytotoxicity paralleled the proportion of effector cells, the cells remaining in the circulation following DEX administration retained normal antibody-dependent cytotoxic capabilities. Neutrophil-mediated ADCC against HRBC significantly increased at 4 h from a geometric mean of 3785 to 20142 lytic units P < 0.02) concomitant with the blood neutrophilia and remained elevated for 72 h. Neutrophil ADCC against Ch and HHC was minimal and was not affected by DEX administration. This study demonstrates differential effects of corticosteroids on antibody-dependent cell-mediated cytotoxicity, reflecting changes in proportion of circulating effector cell populations. These changes depend on (the target cell employed, the effector cell mediating cytotoxicity and the duration of time since the last dose of corticosteroid.