Minipig Model of Atopic Dermatitis: Assessment of In Vivo and In Vitro Activity of Recombinant Porcine Interleukin-4 and Interleukin-13
Jones, M.R., Zhong, M., Johnson, S., Brocksmith, D., Bouchard, G.F., Stricker-Krongrad, A.
Atopic Dermatitis is a common skin condition that clinically presents as erythematic, dry, pruritic skin. Minipigs are used frequently for toxicity/safety of dermally applied products, and thus a model of AD in minipigs would be beneficial for pre-clinical efficacy tests of such medications. This study assessed sensitivity of Hanford minipigs to recombinant porcine (rp) IL-4 and IL-13. Peripheral Blood Mononuclear Cells (PBMC) isolated from female Hanford minipigs demonstrated approximately a 4 fold increase in STAT6 phosphorylation when challenged with rpIL-4, but not rpIL-13. When female Hanfords received a single intradermal dose of rpIL-4 or rpIL-13, erythema and edema was not different from vehicle control dose sites. However, repeat intradermal injections for a period of five days did elicit increased erythema and edema in rpIL-4 dose sites relative to vehicle control, but not rpIL-13 dose sites. The peak irritation was observed approximately 5 minutes after dose administration, similar to histamine injections in minipigs. Interestingly, perivascular or dermal lymphocytes were observed in ~25-38% of rpIL-4 and rpIL-13 dose sites, but were not present in the vehicle control sites. Perivascular eosinophils were observed in ~25% of the rpIL-4 dose sites, while not observed in vehicle or rpIL-13 dose sites. This suggests that intradermal injection of rpIL-4 and rpIL-13 may recruit lymphocytes to dermal tissues. These findings that rpIL-4 and rpIL-13 appear to have biological activity in Hanford minipigs, and are good candidates for further exploration in developing a porcine model of Atopic Dermatitis.