FC‐54 Evaluation of IgE‐mediated late‐phase reactions in the skin of normal placebo‐ and prednisolone‐treated dogs: cellular, cytokine and chemokine responses

IgE-mediated late-phase reactions can be induced in the skin of normal and atopic dogs by intradermal injections of anti-IgE antibody. The histology of these reactions is very similar to that of naturally occurring atopic dermatitis. To characterize the cellular, cytokine and chemokine responses in the skin of placebo- and prednisolone-treated dogs, normal beagles received either placebo or 0.5 mg/kg prednisolone twice daily for three days prior to intradermal injection of polyclonal rabbit anti-canine IgE. Eight-millimetre punch biopsy skin samples were taken before injection and at the injection sites after 6, 24 and 48 h. Histological and immunohistochemical examination revealed a rapid cellular influx. Eosinophil and neutrophil numbers increased from <1 to 61.4 ± 14.1, and from 7 to 62.2 ± 10.8 cells/mm2, respectively, within 6 h after injection, and remained moderately elevated 48 h later. The numbers of CD1c+, CD3+ and CD4+ mononuclear cells were also increased by 6 h. Taqman analysis demonstrated 2.5- to 72-fold increases in mRNA expression for IL-13, IL-5, MCP (CCL2), RANTES (CCL5) and TARC (CCL17). Levels of mRNA for IL-2, IL-4, IL-6, and IFNγ remained negligible. Prednisolone administration suppressed the influx of neutrophils and eosinophils, and the expression of IL-13, CCL2, CCL5 and CCL17 (33, 97, 58, 86, 73 and 90%, respectively), as well as the influx of CD1c+ and CD3+ cells. These data document the cytokine and chemokine response to anti-IgE injection and demonstrate the anti-inflammatory effect of prednisolone. Funding: Schering-Plough Animal Health.