Therefore, although a clinical trial using the anti-IL-6 receptor antibody tocilizumab is underway, it is important to recognize the state of SSc patients prior to selecting treatment.
The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography.
Serum levels of IL-6 were significantly elevated in SSc patients (p = 0.024) and were positively correlated with the modified Rodnan skin score (rs = 0.291, p =0.041).
These results suggest that vasculopathy-induced hypoxia and oxidative stress might enhance ATP release in the dermis in SSc and that extracellular ATP-induced phosphorylation of p38 via P2Y<sub>2</sub> receptor might enhance IL-6 and collagen type I production in SSc fibroblasts.
In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles.
In addition to the profibrotic role of interleukin 6 and transforming growth factor-β, newer studies stress on glycoprotein Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D) and chemokine (C-C motif) ligand 18 (CCL18) as potential biomarkers of skin and lung fibrosis in SSc.<b>Expert opinion</b>: Skin and lung biomarkers in SSc frequently mirror the typical signs of fibrosis, overlapping sporadically.
Classical targets for fibrosis in SSc like transforming growth factor Beta (TGF-β), Interleukin-6 (IL-6), and multiple tyrosine kinases, have not yielded therapeutic benefit.
The profound impact of IL-6R blockade on the activated fibroblast phenotype highlights the potential of IL-6 as a therapeutic target in SSc and other fibrotic diseases.
In unstimulated PBMC, the production of TNF(p = 0.004), IL-10(p = .048), IL-2(p < 0.001), and IL-6 (p = 0.01) was higher in SSc patients than in healthy controls.
There was evidence of altered distribution of transitional B cell subsets, increased production of interleukin-6 (IL-6) and IL-8, and defective tolerance induction in SSc B cells.
Moreover, the role of cytokine (interleukin-1β, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated.
Serum levels of IL-1β, IL-12 and IL-6 in PSS patients were significantly lower than those in controls (P < 0.003), and these associations survived the Bonferroni correction (Pc < 0.018).
A possible role of IL-6 in the regulation of firoblast differentiation and stimulation of collagen synthesis has been suggested and in patients with systemic sclerosis (SSc) the treatment with tocilizumab (TCZ) was associated to improvement of skin thickness and joint motion.
In addition, the levels of IL-6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFβ (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls.
Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc.