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The significance of interleukin-6 and C-reactive protein in systemic sclerosis: a systematic literature review.

OBJECTIVES
Interleukin-6 (IL-6) may play a role in the pathogenesis of SSc. C-reactive protein (CRP), an acute phase reactant induced by IL-6, may be a prognostic marker in SSc. The goal of this systematic review was to address the significance and clinical application of IL-6 and CRP in systemic sclerosis (SSc).


METHODS
A literature search was conducted to identify English-language original articles within PubMed, Scopus, and Medline database from inception to May 30, 2013 using keywords 'systemic sclerosis or scleroderma and C-reactive protein or interleukin-6'.


RESULTS
The search resulted in 156 relevant articles. Some single nucleotide polymorphisms and gene-gene interactions affect SSc predisposition, manifestation and expression of IL-6. Studies in animal models show IL-6 and IL-6 trans-signalling are involved in SSc disease development. Derangements of T and B cells function regulate IL-6 in SSc pathogenesis. Fibroblasts, T/B cells, monocytes, macrophages, dendritic cells and endothelial cells participate in IL-6 expression and interact with each other resulting in tissue sclerosis. Up-regulation of serum IL-6 and CRP levels are evident in SSc patients and associated with disease activity, severity, disability, worse outcome and reduced survival. Targeted IL-6 therapy in SSc has occurred in small cases series and within a multi-site trial that is under way.


CONCLUSIONS
Studies show IL-6 and CRP are important in SSc both in pathogenesis and clinical manifestations and may be useful indicators of disease activity, severity, and poor prognosis. IL-6 could be a relevant treatment target in SSc.