A canine model of cutaneous late‐phase reactions: prednisolone inhibition of cellular and cytokine responses

Abstract

SummaryImmunoglobulin E (IgE)-mediated late-phase reactions can be induced in atopic humans by intradermal injection of relevant allergens or anti-IgE antibodies. The histology of these reactions resembles that of naturally occurring atopic dermatitis. Strikingly similar responses can be induced in dogs, suggesting that a canine model could prove valuable for preclinical investigation of drugs targeting late-phase reactions. This study was designed to characterize the cellular, cytokine and chemokine responses after intradermal anti-IgE injection in untreated and prednisolone-treated dogs. Normal beagles were untreated or treated with prednisolone before intradermal injection of polyclonal rabbit anti-canine IgE or normal rabbit IgG. Biopsies were taken before injection and 6, 24 and 48 hr after injection. Samples were evaluated by histological and immunohistochemical staining, as well as by real-time quantitative polymerase chain reaction analysis. Dermal eosinophil and neutrophil numbers increased dramatically within 6 hr after injection of rabbit anti-canine IgE, and remained moderately elevated at 48 hr. The numbers of CD1c + and CD3 + mononuclear cells were also increased at 6 hr. The real-time quantitative polymerase chain reaction demonstrated marked increases in mRNA expression for interleukin-13 (IL-13), CCL2, CCL5 and CCL17. Levels of mRNA for IL-2, IL-4, IL-6 and IFN-c did not change within the limits of detection. Prednisolone administration suppressed the influx of neutrophils, eosinophils, CD1c + and CD3 + cells, as well as expression of IL-13, CCL2, CCL5 and CCL17. These data document the cytokine and chemokine responses to anti-IgE injection in canine skin, and they demonstrate the ability of the model to characterize the anti-inflammatory effects of a known therapeutic agent.

Characterization of IgE-mediated cutaneous immediate and late-phase reactions in nonallergic horses

“…The anti-IgE injection resulted in increased numbers of CD3 + cells, compared with the number of CD3 + cells after IgG injection, from 20 minutes to 24 hours with a subsequent decrease in cell counts at 48 hours, but these values did not differ significantly ( Figure 5). This pattern was similar to that for a previous study 9 in dogs in which CD3 + cells increased by 6 hours and peaked 24 hours after anti-IgE injection. Another study 8 conducted to evaluate late-phase reactions after ID injection of anti-IgE in dogs found that dermal counts of CD3 + cells increased from 6 to 48 hours after injection.…”

“…[10][11][12][13][14][15][16] In dogs, a model of allergic dermatitis has been successfully developed by the use of anti-IgE. 8,9 To our knowledge, such a model of allergic dermatitis in horses has not been developed.…”

“…Researchers have effectively developed models of cutaneous allergic inflammation in other species, including dogs 8,9 and humans. [10][11][12][13][14][15][16] Briefly, allergic skin disease is often mediated by type I hypersensitivity reactions.…”

Animal Models of Allergic Diseases

“…In this model, pruritus and dermatitis can be elicited after epicutaneous application of house dust mites [75]. Lesions are consistent with naturally occurring AD lesions [76,77] making it a suitable model to test new therapies. No skin barrier defect has been described in this model compared to a control population.…”

Premedication with Montelukast Reduces Local Reactions of Allergen Immunotherapy

“…Probably, they rather depend on the newly synthesized late products of the activated mast cells such as leukotrienes and prostanoids [17] as well as the modulation of the mainly neutrophilic as well as eosinophilic infiltrate of type 1 late-phase reactions [18]. Consistently, the leukotriene antagonist (LT-A) montelukast was shown not to affect or influence the immediate response of skin tests with allergen [19], while repressing, for example, delayed pressure urticaria [20].…”