Inhibitors of T-cell mitogenesis: Effect of mitogen dose

The inhibitory effects of seven compounds (hydrocortisone, histamine, interferon, isoproterenol, norepinephrine, serotonin, and γ-aminobutyric acid) were tested in phytohemagglutinin (PHA)-stimulated cultures of human peripheral blood mononuclear cells as a function of PHA concentration. The cultures stimulated by suboptimal levels of PHA were much more sensitive to inhibition by the added compounds, with the curve of percentage inhibition versus concentration of inhibitor shifted to the left by greater than two orders of magnitude in all cases. At the lower doses of mitogen, concentrations of hydrocortisone, histamine, interferon, and isoproterenol which approach the concentrations of these or analogous compounds in vivo caused significant and substantial inhibition of the mitogen response.