Immunostimulatory sequence CpG elicits Th1-type immune responses in inflammatory skin lesions in an atopic dermatitis murine model.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease, for which no fundamental therapy exists. Immunostimulatory sequence CpG (ISS CpG) has potential in reducing susceptibility to allergic diseases and reversing established allergic reactions.


OBJECTIVE
To investigate the effects of ISS CpG in the prevention and treatment of AD in an AD murine model.


METHODS
BALB/c mice were epicutaneously exposed to ovalbumin (OVA) for 3 or 4 weeks with a 2-week resting period between each exposure week. ISS i.d. injection was given either on the 1st day of each exposure week (in the prevention experiment) or 3 days before and on the 1st, 4th and 7th day of the last exposure week (in the treatment experiment). Skin biopsy and blood were obtained at the end of the experiments.


RESULTS
ISS CpG treatment increased drastically mRNA expression of proinflammatory and Th1-type cytokines and chemokines in OVA-treated skin both in the prevention and treatment experiments. The suppressing effect of ISS CpG on Th2-type cytokines and chemokines was weak and limited to IL-13 and CCL24 in the treatment experiment. No significant reduction in OVA-elicited infiltration of eosinophils and T cells in the skin was seen after ISS administration but infiltration of plasmacytoid dendritic cells was absent in ISS CpG-treated skin. In contrast, ISS injection elicited dramatic infiltration of F4/80+ and CCR5+ cells into the dermis and subcutaneous tissue.


CONCLUSIONS
Due to unwanted side effects and minor beneficial effects in our model, administration of ISS CpG may not be suitable for the treatment of AD in humans.
Wang
Guoying
G
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Fyhrquist-Vanni
Nanna
N
Wolff
Henrik
H
Dieu-Nosjean
Marie-Caroline
MC
Kemeny
Lajos
L
Homey
Bernard
B
Lauerma
Antti I
AI
Alenius
Harri
H
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000943:Antigens, Differentiation; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D007073:Immunoglobulin E; D010047:Ovalbumin