The effect of locally injected vasoactive amines on the elicitation of delayed-type hypersensitivity

In previous work monoamine depletion due to treatment with reserpine was shown to decrease the elicitabiltiy of DTH responses in mice. In addition, treatment with monoamine oxidase inhibitors prevented the reserpine-induced decrease. These findings led to the suggestion that serotonin-induced increased vascular permeability is necessary to the development of DTH reactions, perhaps by allowing bone marrow-derived macrophage precursor cells, which are obligate components of DTH responses, to migrate through specialized venules into the site of the reaction. We have compared classical drug tachyphlaxis (temporary inhibition of the effects of a drug by prior treatment with agonists) to serotonin in vessels of mouse feet with local inhibition of DTH after serotonin pretreatment of mice. During the tachyphylactic period, DTH responses are depressed. This suggests that serotonin-induced tachyphylaxis of local endothelial receptors can be responsible for DTH inhibition. In contrast, local injection of histamine has no effect on DTH and this drug is a much less potent inducer of tachyphylaxis to serotonin-mediated vasoactive reactions. On the other hand, histamine can inhibit in vitro T cell reactions, which are not affected by serotonin. These data help to further the concept that serotonin plays an important role in the regulation of DTH in mice and that it probably does so by acting on vascular endothelium.