Background Substantial evidence supports the implication of immune-activated cells, cytokines and chemokines in the pathogenesis of systemic sclerosis (SSc). In fact, interleukin 6 (IL-6) and IL-8 play a crucial role in immunity and fibrosis, both key aspects of SSc. Recent evidence, suggests that an increase of activated circulating monocytes (Mo) on peripheral blood of SSc patients have a potential role on SSc pathogenesis. This could be the source of macrophages that accumulate in injured areas and are active producers of fibrosis-inducing cytokines.
Objectives Our purpose was to investigate the pattern of expression of IL-6 and IL-8 cytokines by peripheral blood (PB) Mo and to explore clinical associations.
Methods This study included 43 SSc patients and 20 healthy controls (HC). All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc and were classified according to LeRoy et al. as having limited cutaneous SSc (lSSc, n=30) or diffuse cutaneous SSc (dSSc, n=13). A clinical evaluation was made, including disease duration, disease activity as measured by the European Scleroderma Study Group criteria, modified Rodnan skin score (mRSS), digital necrosis and target organs’ involvement. The autoantibody profile was collected from medical records.
Each participant was submitted to a blood sample collection, which was processed according to a protocol, designed to separately analyze the intracellular expression of IL-6 and IL-8 in Mo cells
Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney U-test was used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant.
Results The mean age was 56.7±12.3 and 52.0±10.0 years for SSc patients and HC respectively. Females represented 79.1% of SSc and 80.0% of the control group. The mean disease duration was 9.4±8.3 years, the mean mRSS was 12.0±8.1 and the mean disease activity was 2.8±2.4.
The frequency of circulating IL-6 and Il-8-producing Mo cells was not statistically different between SSc patients and HC.
The percentage of IL-8-producing Mo cells was significantly higher in patients with pulmonary fibrosis (p=0.009). No statistically significant differences were observed between early and late-stage SSc, concerning IL-6 and IL-8 expression among Mo. There were no significant association between disease subset, history of digital necrosis, mRSS or disease activity and the frequency of IL-6 and IL-8 expression among Mo cells.
Conclusions IL-8-producing Mo cells frequency is higher in SSc patients with pulmonary fibrosis, no differences being found between the two clinical subtypes of the disease. These findings support the hypothesis that IL-8 produced by these cellular type may be involved in the pathological process of SSc, regardless of the disease subset.
Ann Rheum Dis. 2011 Jun;70(6):1115-21.
Clin Exp Rheumatol. 2011 Mar-Apr;29(2 Suppl 65):S46-52.
Disclosure of Interest None Declared
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