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The Effect of Physical and Chemical Properties of the Sensitizing Substance on the Induction and Elicitation of Delayed Contact Sensitivity

From the Laboratory of Bacterial Products, Division of Biologics Standards, National Institutes of Health, U.S. Department of Health, Education, and Welfare, Bethesda, Maryland 20014

Abstract

The quantitative relationship between induction and elicitation of delayed contact sensitivity by chemically reactive sensitizers and some of the physicochemical properties of these compounds was investigated. Guinea pigs were sensitized with 5 µmols of compound in complete Freund's adjuvant and skin tested to determine specific and cross-reactivity. The plot of specific sensitivity against a calculated reactivity coefficient was a parabola. Similar plots of specific sensitivity against nonaqueous solubility or oil-buffer partition coefficients were less significant. For a restricted group of sensitizers, the halodinitrobenzenes and dinitrobenzene thiocyanate, specific sensitivity was negatively proportional to chemical reactivity, solubility, and the atomic parameters of the 1-substituent of the benzene ring (atomic number, atomic weight, radius, surface area, volume). Cross-reactions between substituted 2,4-dinitrobenzenes were extensive but not reciprocal, delayed reactions often being elicited best by heterologous compounds. 3,5-Dinitrobenzoyl chloride was a poor sensitizer and showed little cross-reactivity with 2,4-dinitrobenzene derivatives. The mechanisms underlying these observations may be the interaction between the amount of reactive chemical lost from sensitizing depot or skin test site into the blood by solution in plasma and/or reaction with serum protein and the amount remaining capable of reacting with body cells or tissues. The material lost from the sensitizing depot or skin test site may be or become tolerogenic and influence induction and elicitation of delayed hypersensitivity.

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