Increased interleukin-17 production in patients with systemic sclerosis.
OBJECTIVE
To determine the role of a novel T cell-derived cytokine, interleukin-17 (IL-17), which activates fibroblasts and endothelial cells, in the pathogenesis of systemic sclerosis (SSc).


METHODS
We examined IL-17 production by lymphocytes from the peripheral blood (PBL) and from fibrotic lesions of the skin and lungs of SSc patients by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. We also studied the effect of IL-17 on the proliferation of fibroblasts and on the production of cytokines and the expression of adhesion molecules on endothelial cells in vitro.


RESULTS
IL-17 messenger RNA was expressed in unstimulated PBL and lymphocytes from the skin and lungs of SSc patients, but not in similar samples from patients with systemic lupus erythematosus (SLE) or polymyositis/dermatomyositis or from healthy donors. IL-17 levels were also increased in the serum of SSc patients, but not in that of SLE patients or healthy donors. IL-17 overproduction was significantly related to the early stage of SSc, but not to other clinical features of SSc. Moreover, IL-17 enhanced the proliferation of fibroblasts and induced the expression of adhesion molecules and IL-1 production in endothelial cells in vitro.


CONCLUSIONS
IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients. These results suggest that IL-17 overproduction plays an important role in the pathogenesis of SSc, especially in the early stages of the disease, by inducing the proliferation of fibroblasts and the production of IL-1 and the expression of adhesion molecules on endothelial cells.
Kurasawa
K
K
Chiba University School of Medicine, Chiba City, Japan.
Hirose
K
K
Sano
H
H
Endo
H
H
Shinkai
H
H
Nawata
Y
Y
Takabayashi
K
K
Iwamoto
I
I
D000328:Adult; D000368:Aged; D002455:Cell Division; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000097:blood / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000378:metabolism
D020381:Interleukin-17; D012333:RNA, Messenger; D003094:Collagen