Impact of the magnitude of sensitization dose on the incidence and intensity of CHS to dinitrochlorobenzene (DNCB): Insight from ear swelling and challenged-skin draining lymph node response in rats

Abstract

Allergic contact dermatitis (ACD) is a common skin inflammatory disease that develops in hosts sensitized with contact allergens. Elucidation of dose-response relationships represents one of the approaches in studying the type of ACD in humans/animal models, termed as contact hyper-sensitivity reaction (CHS). Such studies have demonstrated that the intensity of sensitization determines the response to elicitation with a contact allergen, but underlying mechanisms are unclear. The aim of this study is to explore the impact of the sensitization on contact hypersensitivity to dinitrochlorobenzene (DNCB) in rats by measuring the incidence and intensity of a challenge response in hosts sensitized with two different doses (i.e. low and high) of this hapten. Assumptions concerning the contribution from the magnitude of sensitization doses were drawn on the basis of effects from the two doses on the measured reaction parameters. Ear swelling and activity of lymph nodes that drain challenged skin (cdLN), including cellularity, proliferation, and effector cytokine IFN gamma and IL-17 production was measured in rats sensitized with 0.4% or 4% DNCB and challenged with a non-irritant (0.13%) dose. Sensitization with 4% DNCB resulted in a greater proportion of rats who responded more intensely (than unsensitized challenged rats) to challenge in terms of ear swelling and increases in cdLN activity (except for IFN gamma). The intensity of cdLN responses was higher in these hosts as well. Among the high-dose-sensitized rats, greater cellularity/proliferation of cells from lymph nodes (sdLN) that drain the high-dose-sensitized skin, as well as higher IL-17 production, was noted compared to what was seen in rats that received low-dose sensitization. In contrast, unchanged spontaneous and even decreased hapten-stimulated IFN gamma production after the high DNCB dose was observed. Based on the data, it seems the impact of magnitude of sensitization dose on CHS might be related to the rise in the proportion of rats that responded to challenge with an increase of dLN activity. Coincidental higher production of IL-17 by dLN cells from the high-dose-sensitized rats and following challenge of these hosts underscored the significance of IL-17 for a CHS to DNCB.