Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor.
Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis.
de Groot
Marjan
M
Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands, m.degroot@amc.uva.nl
Teunissen
Marcel B M
MB
Ortonne
Jean P
JP
Lambert
Julien R
JR
Naeyaert
Jean M
JM
Picavet
Daisy I
DI
Arreaza
M Gladys
MG
Simon
Jason S
JS
Kraan
Maarten
M
Bos
Jan D
JD
de Rie
Menno A
MA
D000328:Adult; D000368:Aged; D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010091:Oximes; D010880:Piperidines / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry
D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides; D010091:Oximes; D010880:Piperidines; D011725:Pyridines; D019713:Receptors, CCR5; C438583:Ancriviroc