The skin irritant, xylol, when applied to the ears of sensitized and reinjected rabbits often causes a severe inflammation with the formation of crusts and destruction of tissue. Dry gangrene of the entire ear tip may result (Figs. 1, 2, and 3).

The same agent, applied in the same dosage and in the same way, to the ears of (1) normal rabbits, (2) normal rabbits injected once with horse serum (serum controls), or (3) sensitized but not reinjected rabbits, causes only a mild inflammation with more or less edema. The inflammation and edema disappear in 2 or 3 days, leaving a practically normal ear.

The ear lesions of the sensitized reinjected rabbits which develop after the application of xylol are interpreted as a primary anaphylactic reaction. This primary anaphylactic reaction is considered the result of a local autoinoculation of the ear tissues with circulating antigen. The local autoinoculation is brought about by the irritant action of the xylol which causes an inflammation and edema of the site of application. An anaphylactic reaction may now occur because the inflamed tissues are more active metabolically than normal tissues and therefore the inflamed cells are affected by more antigen per unit of time than the normal cells. A subliminal concentration of antigen for non-inflamed, sensitized cells may thus become effective when inflamed sensitized cells are concerned.

This process may theoretically occur in any tissue of a sensitized animal which can show an anaphylactic reaction, for example the intestines, lungs, heart, skin, nerves, arteries, etc. It is possible that this interplay of conditions may explain a number of functional abnormalities in the human subject.

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