Mechanism of inhibition of granulopoiesis by ethanol.

The mechanism of inhibition of neutrophilic granulopoiesis by ethanol has not been well characterized. Possible mechanisms investigated include: (a) a direct toxic effect on the granulocyte-macrophage cluster-colony forming unit (CFU-GM), and/or (b) inhibition of production of CFU-GM proliferation stimulating factor activity (CSA) from T lymphocytes (T cells). Addition of as much as 600 mg% ethanol to T-cell- and monocyte-depleted light-density marrow (TMoDLDBM) cells from humans in soft agar cultures which were stimulated with an exogenous source of CSA did not inhibit the CFU-GM proliferation, suggesting that ethanol has no direct toxic effect on the CFU-GM. T cells obtained from the blood of normal humans were cultured in the presence of phytohemagglutinin with 100 to 600 mg% ethanol. Cell-free conditioned media (CM) from these cultures were tested for CSA concentration by their capacity to stimulate proliferation of CFU-GM from human TMoDLDBM or rat whole bone marrow cells. The results indicated that ethanol at a concentration greater than 100 mg% inhibited CSA production from T cells. There was no evidence for production of an inhibitor of CFU-GM proliferation from T cells in the presence of ethanol. These results suggest that the neutropenia which occurs in relation to alcohol abuse may in part be related to decreased CSA production from T cells.