The mechanisms and evaluation of chemically induced allergy.
Many chemicals are able to induce contact allergy, a delayed-type hypersensitivity reaction. Some of these have, in addition, the potential to cause respiratory allergy, an immediate hypersensitivity reaction effected by IgE antibody. The characteristics of immune responses provoked by chemical allergens determine the type of hypersensitivity reaction which will predominate. Recent evidence indicates that contact and respiratory allergens stimulate qualitatively different immune responses in mice consistent with the selective activation of T helper (TH) cell subpopulations. Contact allergens which lack the potential for respiratory sensitization preferentially activate TH1 cells which effect delayed-type hypersensitivity reactions. A soluble product of TH1 cells, interferon gamma (IFN-gamma), inhibits IgE antibody responses, and thereby the induction of respiratory sensitization. Conversely, chemical allergens which are known to cause respiratory hypersensitivity stimulate preferentially TH2-type responses. TH2 cells promote the development of respiratory allergy through the production of interleukin 4 (IL-4), a cytokine which is required for the initiation and maintenance of IgE responses. Although the molecular basis for the selective activation by contact and respiratory allergens of TH1 and TH2 cells, respectively, awaits clarification, these qualitative differences in immune response provide opportunities for the identification and evaluation of chemical sensitizers.
Kimber
I
I
ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Dearman
R J
RJ
D000818:Animals; D004137:Dinitrochlorobenzene / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D010796:Phthalic Anhydrides / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
D004137:Dinitrochlorobenzene; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride