Relationship between cytokine profiles and clinical outcomes in patients with systemic sclerosis

Although the pathogenesis of systemic sclerosis (SSc) remains unknown, cytokine production and release are key events in this autoimmune disease, characterized by T cell activation and auto-antibodies production leading to microvascular damage, inflammation and fibrosis. We review herein experimental and clinical data, aiming to analyze the relationship between cytokine release and SSc pathogenesis. Measurement of circulating or in situ cytokine levels provides evidence for a balance between "Th1/Th2" or "Th17/Treg" cytokines in the development of SSc. Indeed, the Th2 cytokine response, with the production of IL-4, IL-10 and TGF-beta, leads to tissue fibrosis, whereas Th1 and Th17 cytokines promote inflammation in SSc patients. Thus, cytokine levels have been assessed as diagnostic or prognostic markers in SSc patients. Restoration of the Th1/Th2/Th17/Treg balance is one of the hallmarks of treatment effectiveness and development of cytokine modulators could be considered for new therapeutic approaches in SSc patients. (c) 2010 Elsevier B.V. All rights reserved.