Mechanisms by which barbiturates suppress lymphocyte responses to phytohaemagglutinin stimulation.

Certain barbiturates (the intermediate- and short-acting drugs) reduce the growth of PHA-stimulated peripheral blood mononuclear cells, but phenobarbitone (a long-acting drug) is ineffective: replicative growth is more sensitive than activation. This action is associated with a marked reduction in the density of interleukin-2 receptors on the cell membrane and of the numbers of cells expressing them, but the growth rate cannot be restored by supplementation of the tissue culture medium with exogenous interleukin-2. The affected cells show swelling of the mitochondria and cytoplasmic fat globules: the presence of residual bodies and myelin figures indicate an increase in the rate of degradation of organelles. There was no appreciable increase in the number of necrotic cells seen on electron microscopy of cultures exposed to high concentrations of thiopentone or other potent barbiturates, but the presence of debris in the DNA cytogram at 72 h indicated some increase in the death rate of cells exposed to the growth suppressing barbiturates. It would be inadvisable to administer these short- and intermediate-acting barbiturates over long periods, particularly at high dosage, because of the potential danger of iatrogenic immunosuppression.