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. 2011:2011:721608.
doi: 10.1155/2011/721608. Epub 2011 Sep 20.

The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis

Theresa C Barnes  1 , Marina E Anderson, Robert J Moots
Affiliations

The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis

Theresa C Barnes et al. Int J Rheumatol. 2011.

Abstract

Interleukin-6 is currently attracting significant interest as a potential therapeutic target in systemic sclerosis (SSc). In this paper, the biology of interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in SSc is explored. The role of inteleukin-6 classical and trans signalling pathways in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial cell dysfunction, and fibrogenesis is discussed. The existing evidence that interventions designed to block interleukin-6 signalling are of therapeutic relevance in SSc is evaluated.

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Figures

Figure 1
Figure 1
Interleukin-6 trans signalling. IL-6 receptors are expressed on leukocytes including neutrophils, but they are not expressed on tissue-resident cells, for example, endothelial cells. Endothelial cells can respond to IL-6 through the gp130 receptor only when the IL-6 is bound to a soluble IL-6 receptor (sIL-6R). sIL-6Rs are formed by secretion of an alternatively spliced version of the receptor or proteolytic cleavage from the surface of neutrophils. There is also a pool of soluble gp130 (sgp130) which can bind IL-6/sIL6R complexes and prevent them binding to cellular gp130. Therefore, the local concentrations of IL-6, sIL-6R, and sgp130 regulate IL-6 signalling.
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