Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis
Annals of Rheumatic Diseases, 05/21/2012
Khan K et al. – The results confirm the overexpression of interleukin 6 (IL–6) in diffuse cutaneous systemic sclerosis (dcSSc) and support the potential of IL–6 as a surrogate marker for clinical outcome in this disease. The data also provide rationale for clinical studies targeting IL–6 trans–signalling as a potential antifibrotic therapy for systemic sclerosis (SSc).Methods
- Serum IL–6 and soluble IL–6 receptor levels were measured in patients with SSc (n=68) and healthy controls (n=15).
- Associations between serum IL–6 level and C reactive protein, platelet count and key clinical outcomes in SSc were explored.
- Expression of IL–6 in skin biopsies was also examined and western blot and reverse transcription PCRanalysis were performed using cultured dermal fibroblasts.
- The effect of IL–6 trans–signalling on production of extracellular matrix proteins was assessed and downstream signalling pathways were examined using pharmacological inhibitors.
- Serum IL–6 level was frequently elevated in patients with SSc, particularly in those with diffuse cutaneous SSc (dcSSc) with thrombocytosis and elevated acute phase markers.
- Prominent expression in the skin was observed in dermal fibroblasts, mononuclear cells and endothelial cells in patients with early dcSSc.
- In vitro experiments supported a potent profibrotic effect of IL–6 trans–signalling via the JAK2/STAT3 and ERK pathways.
- High IL–6 expression early in dcSSc appears to be associated with more severe skin involvement at 3 years and worse long–term survival than in those without elevated IL–6 levels.