Recombinant murine interleukin 4 protein therapy for psoriasis in a transgenic VEGF mouse model.
BACKGROUND
Psoriasis is a typical autoimmune disease caused by a deregulation of the Th1/Th2 balance, and immunotherapy for psoriasis has been shown to be clinically efficacious. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. Evidence suggests that the chronic delivery of VEGF to the skin can result in a profound inflammatory condition with many of the cellular and molecular hallmarks of human psoriasis. In this study, we investigated whether the transgenic VEGF mouse is a suitable model for antipsoriatic studies.


OBJECTIVE
To determine the effect of a recombinant murine interleukin 4 (rmIL-4) in the transgenic VEGF mouse model.


METHODS
Fifteen homozygous K14-VEGF transgenic mice were injected subcutaneously with rmIL-4 protein for 30 consecutive days with a prospective dose escalation of 0.5, 2 or 5 microg/kg. Hematoxylin-eosin staining, immunohistochemistry and real-time polymerase chain reaction analyses were performed with ear samples.


RESULTS
The rmIL-4 protein therapy was well tolerated. Tissue sections from treated skin showed improvements upon morphological and histological examinations: diminution of erythematous appearance and regression of epidermal thickness were observed, and T lymphocyte infiltration decreased significantly. The expressions of adhesion molecules, such as vascular cell adhesion molecule 1 and intracellular adhesion molecule 1, were found reduced. The level of IL-4 mRNA also increased while the level of gamma-interferon mRNA decreased, resulting in a 10-fold increase in the ratio of Th1/Th2.


CONCLUSIONS
Our results reveal that rmIL-4 has clinical efficacy for the treatment of K14-VEGF transgenic mice. Angiogenesis and inflammation were ameliorated by therapy with rmIL-4.
Ren
Xiaoxiao
X
State Key Laboratory of Biotherapy, West China Hospital and School of Life Science, Sichuan University, Chengdu, China.
Li
Jiong
J
Zhou
Xikun
X
Luo
Xiaolei
X
Huang
Nongyu
N
Wang
Yongsheng
Y
Chen
Xiancheng
X
Wei
Yuquan
Y
D000818:Animals; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D015870:Gene Expression; D007150:Immunohistochemistry; D007267:Injections; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D007371:Interferon-gamma