Critical contribution of the interleukin-6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis.
Reflecting the critical role of interleukin (IL)-6 in systemic sclerosis (SSc), tocilizumab, an anti-IL-6 receptor antibody, is currently under a global phase III trial against skin sclerosis of this disease. We here demonstrate that the IL-6/signal transducer and activator of transcription 3 axis is broadly activated in various cell types in the lesional skin of SSc patients irrespective of disease subtypes, especially in endothelial cells. Importantly, 12 monthly infusions of tocilizumab improved nailfold capillary changes as well as skin sclerosis in a patient with diffuse cutaneous SSc. The present findings suggest a potential disease-modifying effect of tocilizumab on SSc vasculopathy.
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Takashi
T
Taniguchi
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Yoshihide
Y
Asano
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Takemichi
T
Fukasawa
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Ayumi
A
Yoshizaki
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Shinichi
S
Sato
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D002196:Capillaries / Q000000981:diagnostic imaging / Q000187:drug effects; D046169:Dermoscopy; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000098:blood supply / Q000000981:diagnostic imaging; D010865:Pilot Projects; D051789:Proto-Oncogene Protein c-fli-1; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014652:Vascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*
D061067:Antibodies, Monoclonal, Humanized; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D051789:Proto-Oncogene Protein c-fli-1; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C502936:tocilizumab
interleukin-6; signal transducer and activator of transcription 3; systemic sclerosis; tocilizumab; vasculopathy