Cellular and cytokine kinetics after epicutaneous allergen challenge (atopy patch testing) with house dust mites in high‐IgE beagles

Abstract

The cellular and cytokine dynamics of reactions triggered by atopy patch testing with house dust mites were studied in six high-IgE beagles. Sites were scored and biopsied at 6, 24, 48, and 96 h, and samples were processed for histopathology, immunohistochemistry, and polymerase chain reaction (PCR). All dogs developed positive reactions at some point in time. Mean clinical scores were significantly higher than baseline at 24, 48, and 96 h. Clinically, one of six dogs had a positive reaction at 6 h; two of six reacted at 24 and 48 h, and five of six at 96 h. Histologically, superficial perivascular mononuclear and granulocytic dermatitis developed (5/6) after 6 h, and progressed in severity at 24 h (6/6). Additionally, at 48 h epidermal spongiosis, hyperplasia and pustules developed (5/6), and were marked at 96 h (6/6). At and beyond 6 h, progressive CD1c-positive epidermal Langerhans cell hyperplasia with cluster formation and dermal dendritic cell infiltration was noted. Cutaneous infiltration of CD3-positive T lymphocytes with epidermal clusters developed over time. mRNA expression for the cytokines gamma-interferon (gamma-IFN), interleukin-6 (IL-6), IL-12p35, IL-13, IL-18, and thymus and activation regulated chemokine (TARC) exhibited significant increases during the challenge compared to baseline, but there was no appreciable alteration in expression for tumour necrosis factor-alpha (TNF-alpha), IL-12p40, IL-10, regulated on activation normal T-cell expressed and secreted (RANTES), IL-5, IL-2, IL-4, and IL-8. No correlation was detected between clinical scores and cytokines. It is concluded that IL-6 plays a role in early reactions followed by an increase of TARC and IL-13, while IL-18 progressively increases in later reactions.

Characterisation of T cell phenotypes, cytokines and transcription factors in the skin of dogs with cutaneous adverse food reactions

“…NLS skin had increased expression of IL- 4 and Foxp3, which may indicate that NLS skin is primed to become LS skin. In comparison, the cutaneous inflammation in dogs with spontaneous AD was characterised by expression of IL-6, TARC, IL-4 and IL-13 mRNA in the early stages, and IFN-c, IL-12 and IL-18 in the chronic stages and no data are available on Foxp3 expression levels (Olivry et al, 1999;Nuttall et al, 2002;Marsella et al, 2006 (Cosmi et al, 2003;Jarvis et al, 2005;James and Kwok, 2007;Joosten et al, 2007;Mahic et al, 2008;Billerbeck et al, 2009). It would be interesting to investigate whether the CD8 + T cells are responsible for…”

“…In contrast, cell subsets and cytokine production in the skin of dogs with AD have been investigated extensively. In AD, inflammation is characterised by an influx of CD4 + and CD8 + T cells in the lesional skin (Olivry et al, 1997;Sinke et al, 1997) and a mixed cytokine profile with predominant expression of IL-6, TARC, IL-4 and IL-13 genes in the early stage followed by IFN-c, IL-12 and IL-18 later on (Olivry et al, 1999;Nuttall et al, 2002;Marsella et al, 2006). Whereas most dogs with AD have circulating allergen-specific IgE (DeBoer and Hillier, 2001), there is controversial evidence for a similar reaction phenomenon in dogs with spontaneous manifestations of CAFRs (Jackson et al, 2003;Pucheu-Haston et al, 2008;Puigdemont et al, 2006).…”

Molecular Cloning of Canine Protease-Activated Receptor-2 and its Expression in Normal Dog Tissues and Atopic Skin Lesions

“…Furthermore, epicutaneous sensitization with HDM allergens has been shown to induce elevation of mite-specific IgE and pruritic dermatitis, resembling spontaneous AD in dogs [19]. Additionally, atopy patch testing with HDM enhanced mRNA transcription of cytokines (IL-6, IL-12p35, IL-13, IL-18 and IFN-) and a chemokine, TARC/CCL17, in lesional skin from high-IgE Beagles [12]. Lymphocytes and keratinocytes, the principle epidermal cells, have been recognized as a major source of cytokine production [8].…”

Clinical and Immunologic Effects of Allergen-Specific Sublingual Immunotherapy in a Canine Model of Atopic Dermatitis: A Double Blind, Randomized, Controlled Study

“…Clinical monitoring: Clinical evaluation was done using a modified version of the validated Canine Atopic Dermatitis Extent and Severity Index Score 03 (CADESI) [23]. The two modifications in relation to CADESI-03 were that papules were added as a clinical sign and that the scores for each sign ranged from 0 to 3 rather than from 0 to 5 [28].…”

“…Dogs are closer to humans than mice and share the same environment with humans thus making them an ideal choice for a model. An experimental model for AD has been validated using atopic Beagles [21][22][23]. Symptoms of AD in both species include recurrent pruritic dermatitis affecting the flexural surfaces, periocular, perioral, axillary, and inguinal areas.…”