gms | German Medical Science

Introduction: Systemic sclerosis (SSc) is an autoimmune connective tissue disease defined by fibrosis of skin and internal organs as well as vascular impairment accompanied by a significantly higher mortality rate than in the general population. Therefore, early severe courses of SSc should be provided for intensified treatment such as hematopoetic stem cell transplantation (autoTx). In addition to the fibrosis several features of SSc often show a phenotype of auto-inflammation which is thought to be mediated by the TH17 pathway in addition to other inflammatory factors [1].

Methods: Here we investigated cultures of skin fibroblasts derived from SSc (3 to 6 months) after successful autoTx as well as without autoTx compared to healthy controls (HC) to evaluate the different expression of pro-inflammatory cytokines (interleukin-1-beta, interleukin-6 (IL-6), interleukin-8 (IL-8)) after stimulation of interleukin-17 (IL-17) and combined with tumor growth factor-beta (TGF-beta), measured by concentrations (ng/ml, +/-standard error) in the cellular supernatant using ELISA tests. SSc patients (n=8, aged 43 to 65 years), three of them after autoTx (n=3, aged from 54 to 59 years) and healthy controls (n=4, aged 40 to 53 years) underwent a skin biopsy of the lateral abdominal wall or forearm. The cells were stimulated by 25 ng/ml of IL-17 and 2.5 ng/ml of TGF-beta for 48 h. The differences between SSc, SSc after autoTx and HC were statistically analysed by t-test (with fisher’s correction).

Results: IL-8 and IL-6 secreted by native fibroblasts showed a significantly higher concentration in SSc compared to HC after IL-17 stimulation (figure 1 [Fig. 1]); in addition, the IL-8 and IL-6 concentrations after autoTx developed to the level of HC being significantly lower compared to SSc without autoTx (figure 1 [Fig. 1]). After IL-17 stimulation together with TGF-beta the concentration of IL-8 (but not IL-6) concentrations also resulted in significantly higher values for SSc fibroblasts compared to HC as well as SSc patients after autoTx (1.99+/-0.23 vs. 0.47+/-0.07 [p=0.0007] vs. 0.63+/-0.06 [p=0.0008]). IL-1beta did show any differences between the subgroups (data not shown).

Conclusion: Skin fibroblasts in SSc patients showed significantly stronger IL-6 and IL-8 driven pro-inflammatory properties than HC, in particular, after stimulation IL-17; furthermore, the secretion of IL-6 and IL-8 by SSc skin fibroblasts seems to be reduced by the hematopoetic stem cell transplantation to the level of HC. In what way IL-6 and IL-8 may be a potential biomarker for disease activity of SSc remains the subject of further research.