Inhibitory effects of corticosteroids and histamine on human lymphocytes

Both corticosteroids and histamine inhibit mitogen-induced lymphocyte proliferation. Their mechanisms of inhibition were studied in lymphocytes exposed to methylprednisolone (MP) both in vivo and in vitro. Either in vivo MP treatment or in vitro histamine incubation depressed lymphocyte responsiveness to mitogen stimulation. The combination of both treatments depressed the proliferative responses to a further degree, representing a shift of baseline proliferation by in vivo MP treatment. For in vitro MP studies, normal lymphocytes cultured with varying concentrations of MP were significantly less stimulated by phytohemagglutinin (PHA) and concanavalin A (Con A). Addition of histamine (1 x 10(-3) M) as well as MP in vitro led to a further inhibition of proliferative responses of these cells in an additive pattern in cultures of all MP concentrations. Normal lymphocytes incubated in vitro with histamine, but not with MP, resulted in a rapid rise in intracellular cyclic adenosine monophosphate (cAMP). These findings suggest that corticosteroid and histamine act independently through different mechanisms.