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Effects of pentoxifylline on immediate and late-phase cutaneous reactions in response to anti–immunoglobulin E antibodies in clinically normal dogs

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  • 1 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 2 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 3 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 4 Division of Laboratory Animal Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
  • | 5 Division of Laboratory Animal Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
  • | 6 Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

Objective—To characterize the effects of pentoxifylline on the gross and microscopic variables associated with immediate and late-phase inflammation following injection of IgE-specific antibodies in the skin of clinically normal dogs.

Animals—6 healthy adult mixed-breed dogs.

Procedures—Intradermal injections (0.1 mL each) of PBS solution, histamine phosphate, and cross-linking rabbit-origin anti-canine IgE antibodies (3 injections/dog) were administered at 0 hours on day 0; wheal sizes were evaluated at 20 minutes, 6 hours, and 24 hours. Biopsy specimens of injected and noninjected skin were collected 24 hours after injection. On day 2, treatment with pentoxifylline (20 mg/kg, PO, q 8 h) was initiated and continued until day 30. For each dog, injection, measurement, and biopsy procedures were repeated on days 30 to 31 and on days 37 to 38 (ie, after discontinuation of pentoxifylline administration).

Results—Pentoxifylline administration was associated with a significant decrease in wheal size at 6 and 24 hours (but not at 20 minutes) after injection of anti-canine IgE. Repeated injections performed 1 week after drug discontinuation revealed partial recovery of the 6-hour cutaneous reaction and complete recovery of the 24-hour cutaneous reaction. Pentoxifylline administration was also associated with inhibition of mast cell degranulation and significant decreases in the total numbers of cutaneous inflammatory cells and eosinophils, compared with pretreatment findings.

Conclusions and Clinical Relevance—In clinically normal dogs, pentoxifylline effectively impaired late-phase reactions but not immediate reactions at sites of intradermal injection of IgE-specific antibodies by inhibiting mast cell degranulation and recruitment of cutaneous inflammatory cells, especially eosinophils.

Contributor Notes

Supported by an NIH T35 training grant (TRR017504B) and the Louisiana State University School of Veterinary Medicine Department of Veterinary Clinical Sciences.

The authors declare that they have no conflicts of interest.

Presented as a poster at the Merial-NIH Veterinary Scholars Symposium, Fort Collins, Colo, August 2012, and at the Phi Zeta Research Emphasis Day at Louisiana State University, Baton Rouge, La, September 2012.

Address correspondence to Dr. Pucheu-Haston (cpucheu@lsu.edu).