The antihistamine, triprolidine, was tested for its capacity to suppress the increased capillary permeability in active, direct passive and reversed passive cutaneous anaphylaxis in guinea pigs. Whereas triprolidine caused a 500- to a 5000-fold suppression of the permeability response to intracutaneously injected histamine, it was never capable of suppressing the anaphylactic response more than 10-fold. In four out of eight experiments, the suppression of anaphylaxis was less than 2-fold, a difference shown to be within the range of experimental error.

Our findings fail to support the notion that histamine is an important mediator in cutaneous anaphylaxis. On the contrary, they indicate that histamine plays little or no role in the events leading to the increase in capillary permeability in cutaneous anaphylaxis, regardless of its presumed role in other manifestations of immediate hypersensitivity.

We have stressed the point that individual variation in the anaphylactic response must be taken into account in assessing the possible suppressive effect of an antagonist. To be considered significant, the degree of suppression must fall beyond the limits of this variability. In these experiments, the effects of inter-animal variation were minimized by comparing the means of responses in groups of animals. Furthermore, the degree of suppression of anaphylaxis was viewed in relation to the suppression of the response to histamine in the same animals. The relatively slight differences in the anaphylactic response between triprolidine-treated and control animals could have arisen from normal variation. The histamine response, however, was always suppressed to a degree far beyond the limits of natural variability. If histamine were an important mediator in the permeability response in cutaneous anaphylaxis, one might expect a potent antihistamine to suppress the anaphylactic response to a degree at least approaching the magnitude of the 500- to 5000-fold suppression of histamine.

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