The effects of gene gun delivered pIL-3 adjuvant on skin pathology and cytokine expression.
The aim of this study was to investigate skin immunopathology following gene gun delivery of plasmid-encoding interleukin 3 (pIL-3) and hence explore the possible mechanisms of its adjuvant activity. Using the sheep as the experimental model, expressible pIL-3 was administered to the epidermis and the dermal/epidermal junction and its effects on the skin were assessed by histopathology, immunohistology and quantitative RT-PCR for a range of pro-inflammatory and immune response polarizing cytokines. Delivery of both functional and non-functional plasmids caused an acute inflammatory response with the infiltration of neutrophils and micro-abscess formation; however, the response to pIL-3 was more severe and was also associated with an early (24 h) infiltration of B cells and a later accumulation of CD172a-/CD45RA+ dendritic cells (DC). In terms of cytokine transcript expression, an early TNFalpha response was stimulated by gene gun delivery of plasmid-associated gold beads, which coincided with an immediate infiltration of neutrophils. However, only pIL-3 triggered the short-lived expression of IL-3 (peaking at 6 h) and significant long-term increases in both TNFalpha and IL-1beta. pIL-3 did not affect the expression of the immune response polarizing cytokines, IL-10 and IL-12.
Matthews
K
K
Centre of Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
Rhind
S M
SM
Gossner
A G
AG
Dalziel
R G
RG
Hopkins
J
J
D000276:Adjuvants, Immunologic; D000818:Animals; D019470:Biolistics / Q000662:veterinary*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007377:Interleukin-3 / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D010957:Plasmids / Q000235:genetics; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology / Q000662:veterinary*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007377:Interleukin-3