Studies on the Eczematous Sensitization Iv. Sensitization to Metadinitrobenzene and Its Relation to 2:4 Dinitrochlorobenzene*

In the study of sensitizations to simple chemicals, there are two somewhat related chemical problems. One is the nature of the union between the sensitizing chemical and the tissues of the host in order to engender the eczematous sensitization, and the other is in what chemical respects can a substance that is capable of evoking a reaction in the already sensitized animal deviate from the parent sensitizing compound? It has been reasonably well shown, originally by Landsteiner (1) and subsequently confirmed by others, that simple chemical compounds which are capable of inducing the eczematous variety of the delayed type of allergic sensitization enter into some sort of union with the tissues of the host. The simplest hypothesis is that a protein conjugate is made. There seems to be direct chemical evidence for this type of union with certain classes of compounds, such as substituted nitroand halo-benzenes, especially the dinitrophenyls. Such a union may not be true for all substances which yield an eczematous sensitization, e.g., nickel, for, as GeIl (2) states: "Many chemical compounds which act as sensitizers have one general feature in common: they are capable of reacting with a group or groups in the molecule of a protein to form a conjugate. A second type of sensitizer is not able itself to combine with protein, but may be metabolized in the body to a derivative possessing such powers of combination. There may be a third category of sensitizers which do not react chemically but form strong adsorption complexes with protein. In any case the conjugate or adsorption complex so formed will become aritigenically distinct from the parent protein, and if the sensitizer gains access to the tissues of an animal the proteins of the latter may be rendered antigenic." Much less work has been done to determine how far and in what respect one can deviate chemically from the compound to which the host was originally sensitized and still obtain a reaction. Rostenberg and Kanof (3) studied this problem in persons who had been sensitized to 2:4 dinitrochlorobenzene and came to the conclusion that "in the case of the substituted halo-benzenes, for the body to react to a compound other than the one to which it is sensitized, it appears that two factors must be present: 1) a geometric resemblance of the original to the new compound; and 2) the new compound must be capable of forming conjugates of a kind similar to the original." Subsequently Eisen and colleagues (4) in several studies have furnished rather detailed knowledge concerning the nature of the union and the chemical dif-