Histamine-induced regulation of IL-2 synthesis in man: Characterization of two pathways of inhibition

Histamine at molar concentrations ranging from 10⁻⁵ to 10⁻⁷ exerted an inhibitory effect upon IL-2 synthesis by peripheral blood mononuclear cells in normal man; two pathways of inhibition are described. The first pathway was found to alter the T4 lymphocytes which, in the system used in this study, synthesized nearly 90 % of the total IL-2 production and had no suppressive activity. This suggests that histamine can act at the level of IL-2-producing cells. The second pathway of inhibition was related to induction of suppressor cells. Peripheral blood lymphocytes pre-incubated for 1 h with histamine 10⁻⁵–10⁻⁷ M inhibited the IL-2 synthesis of normal autologous lymphocytes in a co-culture system. This activity was radio-resistant (1200 r) and mediated by T8 lymphocytes. These two pathways of inhibition were mediated by the specific interaction of histamine with H1- and H2-receptor-bearing mononuclear cells.