Anamnestic responses to contact allergens: Application in the murine local lymph node assay

Abstract

The murine local lymph node assay, an alternative predictive test for the identification of contact sensitizing chemicals, is based upon the fact that skin allergens induce proliferation in lymph nodes draining the site of application. In the present study we have examined whether pre-exposure to the test chemical at a distant site enhances subsequent draining lymph node cell proliferation and, thereby, the sensitivity of the assay. Experiments were performed using both in vitro and in situ measurement of induced lymph node cell proliferation. It was found that, with the exception of potent skin sensitizers such as picryl chloride and oxazolone, which impair subsequent proliferative activity as a consequence of induced immunoregulatory processes, pre-treatment with the test allergen resulted in enhanced proliferation. Evidence is presented that the local lymph node assay response to a variety of skin allergens (including eugenol, isoeugenol, dihydrocoumarin, 4-vinylpyridine, cinnamic aldehyde and 2,4,5-trichlorophenol) was augmented when mice received a single exposure to the same chemical 5 days earlier. It is concluded that the use of a modified protocol, incorporating pre-exposure to the test material, can enhance local lymph node assay responses to all but the most potent skin allergens, and may be of particular value when increased sensitivity is required.

A sensitive mouse lymph node assay with two application phases for detection of contact allergens

“…Pre-application of strong sensitizers, such as oxazolone and DNCB, depressed LNC proliferation to subsequent application of same chemicals (Miller and Claman 1976;Moorhead 1976;Asherson et al 1977;Thomas et al 1979;Kimber et al 1987Kimber et al , 1989bKimber and Weisenberger 1991). In our assay, compared with intradermal injection of vehicle-FCA emulsion, injection of 0.01 -1% DNCB-FCA emulsion before topical application of DNCB induced higher cpm values (Table 9).…”

“…As injection of FCA into the region caused lymph node activation even in the control group, low SI values were recorded (Tables 3, 4). Kimber and Weisenberger (1991) reported that topical pre-exposure of mice to test chemical on the abdomen enhanced subsequent LNC proliferation. Therefore, we changed the injection site from the scapular region to the abdomen, and attempted to increase LNC proliferation by additional topical application of the chemical to the ears after injection.…”

“…Kimber and Weisenberger (1991) reported that pre-exposure to test chemical at a distant site enhanced subsequent draining LNC proliferation. We next changed the injection site to abdomen.…”

Quantitative relationship between the local lymph node assay and human skin sensitization assays

“…Basketter (2003); Gerberick et al (1992); Hilton et al (1998); Sailstad et al (1995) 1073 Marzulli and Maibach (1974) Glyoxal (107- (2003); Basketter et al (1994Basketter et al ( , 2001b; Basketter and Kimber (2001); Basketter and Scholes (1992); Montelius et al (1994) 3937 4311 Jordan and King (1977); Ford et al (1988); Marzulli and Maibach (1980); Steltenkamp et al (1980b) Imidazolidinyl urea (39236-46-9) 6952 Basketter (2003); Basketter and Scholes (1992) 3846 Jordan and King (1977) Isoeugenol (97-54-1) 524 Basketter (2003); Basketter and Kimber (2001); Basketter and Scholes (1992); Kimber and Weisenberger (1991); Loveless et al (1996); Wright et al (2001) 657 Marzulli and Maibach (1980); Thompson et al (1983) Kanamycin (59-01-8) 2075…”