A canine model of cutaneous late-phase reactions: prednisolone inhibition of cellular and cytokine responses.
Immunoglobulin 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-gamma 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.
Pucheu-Haston
Cherie M
CM
North Carolina State University, College of Veterinary Medicine, Department of Population Health and Pathobiology, Raleigh, 27606, USA.
Shuster
Dale
D
Olivry
Thierry
T
Brianceau
Philippe
P
Lockwood
Patrick
P
McClanahan
Terrill
T
de Waal Malefyt
Rene
R
Mattson
Jeanine D
JD
Hammerberg
Bruce
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D016130:Immunophenotyping; D007271:Injections, Intradermal; D008297:Male; D008407:Mast Cells / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D011239:Prednisolone / Q000627:therapeutic use*; D012867:Skin / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D007073:Immunoglobulin E; D011239:Prednisolone