Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis.
Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic trial in a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun (DKO*) in the epidermis of adult mice leads to a psoriasis-like phenotype with hyper- and parakeratosis and increased subepidermal vascularization. Moreover, an inflammatory infiltrate and elevated levels of cytokines/chemokines including TNFalpha, IL-1alpha/beta, IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and IL-12p40 are detected. Here we show that anti-VEGF antibody treatment of mice already displaying disease symptoms resulted in an overall improvement of the psoriatic lesions leading to a reduction in the number of blood vessels and a significant decrease in the size of dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated mice showed a pronounced reduction of inflammatory cells within the dermis and a normalization of epidermal differentiation. These results demonstrate that systemic blockade of VEGF by an inhibitory antibody might be used to treat patients who have inflammatory skin disorders such as psoriasis.
Schonthaler
Helia B
HB
Banco Bilbao Vizcaya Argentaria (BBVA)-Foundation, Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas, 28029 Madrid, Spain.
Huggenberger
Reto
R
Wculek
Stefanie K
SK
Detmar
Michael
M
Wagner
Erwin F
EF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000517:prevention & control; D042601:Lymphatic Vessels / Q000187:drug effects; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A