Barbiturate inhibition of lymphocyte function. Differing effects of various barbiturates used to induce coma

The present studies evaluated the effect of phenobarbital, pentobarbital, and thiopental at concentrations comparable to those attained during therapeutic barbiturate-induced coma, on in vitro mitogen-induced lymphocyte activation. Lymphocytes from normal volunteers were incubated for 72 hours in culture medium containing mitogen (phytohemagglutinin) and a range of concentrations of the barbiturates (5 to 833 microgram/ml). Three parameters of lymphocyte activation (mitogen-induced blast transformation, 3H-thymidine incorporation, and cell proliferation) were all suppressed by the barbiturates. The suppression was dose-dependent. The greatest suppression was caused by the short-acting barbiturate, thiopental. Lymphocyte responses were much less affected by the long-acting barbiturate, phenobarbital. The intermediate-acting barbiturate, pentobarbital, was also intermediate in its ability to inhibit lymphocyte activation. The two-to threefold difference between the effects of thiopental and pentobarbital on lymphocyte function may have direct clinical relevance, since it is primarily these two agents that are employed to induce therapeutic "barbiturate coma." Since lymphocyte suppression appears to be much more marked in the presence of thiopental, these observations support a role for the other barbiturates in programs of induced coma.