Document Detail

Longitudinal analysis of serum cytokine concentrations in systemic sclerosis: association of interleukin 12 elevation with spontaneous regression of skin sclerosis.
MedLine Citation:
PMID:  16465658     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Skin sclerosis that progresses in the earlier disease phase in systemic sclerosis (SSc) spontaneously regresses thereafter. We investigated the relationship between changes of the serum cytokine profile and changes in skin fibrosis in patients with SSc. METHODS: Serum cytokine levels were examined by ELISA using 180 sera samples from 26 patients with early diffuse cutaneous SSc (dcSSc) with mean disease duration of 2.1 years. The mean followup period was 4.9 years (range 2-8). Cytokine mRNA expression in the affected skin was quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: Modified Rodnan total skin thickness score decreased after 2, 4, and 6 years compared to that at first visit. Serum levels of the Th2 cytokines interleukin 6 (IL-6) and IL-10 and monocyte chemotactic protein-1 (MCP-1) were higher at first evaluation compared to healthy controls, while IL-4 levels were normal. Levels of all Th2 cytokines generally decreased as skin sclerosis regressed. Conversely, levels of serum IL-12, a Th1-inducing cytokine, were lower at first visit relative to controls, but increased by roughly 15-fold after 6 years to significantly higher levels than controls. Surviving dcSSc patients exhibited elevated IL-12 levels compared to deceased patients. Serum levels of transforming growth factor-ss1 (TGF-ss1), a fibrogenic cytokine, increased throughout followup, with slightly decreased levels at later timepoints. IL-12 mRNA expression was upregulated in affected skin from patients with late-stage dcSSc, while TGF-ss1 and MCP-1 expression was downregulated. CONCLUSION: These results suggest that a shift from Th2 to Th1 response correlates with improvement in skin fibrosis in SSc, and that IL-12 level is a serologically useful marker for disease activity and prognosis.
Takashi Matsushita; Minoru Hasegawa; Yasuhito Hamaguchi; Kazuhiko Takehara; Shinichi Sato
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of rheumatology     Volume:  33     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-08     Completed Date:  2006-05-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  275-84     Citation Subset:  IM    
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan.
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MeSH Terms
Chemokine CCL2 / blood,  genetics
Fibrosis / pathology
Gene Expression
Interleukin-10 / blood,  genetics
Interleukin-12 / blood*,  genetics
Interleukin-6 / blood,  genetics
Longitudinal Studies
Middle Aged
RNA, Messenger / metabolism
Remission, Spontaneous*
Reverse Transcriptase Polymerase Chain Reaction
Scleroderma, Systemic / blood*,  pathology
Skin / pathology*
Transforming Growth Factor beta / blood,  genetics
Transforming Growth Factor beta1
Reg. No./Substance:
0/CCL2 protein, human; 0/Chemokine CCL2; 0/Interleukin-6; 0/RNA, Messenger; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12

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