title: Induced changes in total serum IgE concentration in the Brown Norway rat: potential for identification of chemical respiratory allergens.
abstract: A variety of chemicals can cause sensitization of the respiratory tract and occupational asthma that may be associated with IgE antibody production. Topical exposure to chemical respiratory allergens such as trimellitic anhydride (TMA) has been shown previously to induce increases in the total serum concentration of IgE in BALB/c strain mice. Contact allergens such as 2,4-dinitrochlorobenzene (DNCB), which apparently lack respiratory sensitizing potential, fail to provoke similar changes. However, it became apparent with time that there was some inter-animal variation in constitutive and inducible IgE levels. We have now examined the influence of topical exposure to TMA and DNCB on serum IgE levels in the Brown Norway (BN) rat. Such animals can be bled serially and thus it is possible to perform longitudinal analyses of changes in serum IgE concentration. The kinetics of IgE responses therefore can be followed on an individual animal basis, allowing discrimination between transient and sustained increases in serum IgE concentration. Rats (n = 5) were exposed on shaved flanks to 50% TMA, to 1% DNCB (concentrations that elicit comparable immune activation with respect to draining lymph node cellularity and proliferation) or to vehicle alone. Total IgE was measured by enzyme-linked immunosorbent assay in serum samples taken prior to and 14-42 days following initial exposure. Those animals having high pre-existing IgE levels (>1.0 microg ml(-1)) were excluded from subsequent analyses. The levels of serum IgE in the majority of rats exposed to DNCB or vehicle alone remained relatively stable throughout the duration of all the experiments conducted, although some animals displayed transient increases in serum IgE. Only TMA treatment was associated with a significant and sustained increase in the level of serum IgE in the majority of experiments. The elevated concentrations of IgE induced by topical exposure to TMA are persistent, the results reported here demonstrating that induced changes in IgE are maximal or near maximal at approximately 35 days, with a significant increase in IgE demonstrable for at least 42 days following the initiation of exposure. Interestingly, although TMA and DNCB at the test concentrations used were found to be of comparable overall immunogenicity with regard to lymph node activation and the induction of lymph node cell proliferation, there were apparent differences in humoral immune responses. Thus, not only did exposure to TMA stimulate increases in total serum IgE concentration and the production of specific IgE antibody, but also a more vigorous IgG antibody response was provoked by TMA compared with DNCB. These data suggest that the measurement of induced changes in serum IgE concentration in the BN strain of rat is able to differentiate between different classes of chemical allergen. Given the inter-animal variation in IgE production, it would be prudent to incorporate a concurrent assessment of responses induced by treatment with TMA as a positive control against which to assess the activity of other test materials.
authors.affiliation: Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK.
authors.forename: E V
authors.initials: EV
authors.lastname: Warbrick
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: I
authors.initials: I
authors.lastname: Kimber
mesh_terms: D000287:Administration, Topical; D000393:Air Pollutants / Q000276:immunology; D000395:Air Pollutants, Occupational / Q000276:immunology; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D000393:Air Pollutants; D000395:Air Pollutants, Occupational; D000485:Allergens; D004137:Dinitrochlorobenzene; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride