Supplementary Material for: Environmental and Genomic Factors as well as Interventions Influencing Smoking Cessation: A Systematic Review of Reviews and a Proposed Working Model

<b><i>Background:</i></b> Smoking behaviour is a major public health problem worldwide. Several sources have confirmed the implication of genomic factors in smoking behaviour. These factors interact both with environmental factors and interventions to develop a certain behaviour. <b><i>Objectives:</i></b> Describing the environmental and genomic factors as well as the interventions influencing smoking cessation (SC) and developing a working model incorporating the different factors influencing SC were our main objectives. <b><i>Methods:</i></b> Two systematic reviews were conducted using articles in English from the Cochrane library, PubMed and HuGENet from January 2000 to September 2012: (1) a systematic review of systematic reviews and meta-analyses and (2) a systematic review of original research for genomic factors. The proposed working model was developed by making use of previous models of SC and applying an iterative process of discussion and re-examination by the authors. <b><i>Results:</i></b> We confirmed the importance of the 4 main factors influencing SC: (1) environmental factors, (2) genomic factors, (3) gene-environment interactions, and (4) evidence-based interventions. The model demonstrates the complex network of factors influencing SC. <b><i>Conclusion:</i></b> The working model of SC proposed a global view of factors influencing SC, warranting future research in this area. Future testing of the model will consolidate the understanding of the different factors affecting SC and will help to improve interventions in this field

Supplementary Material for: Induction of Myeloid-Derived Suppressor Cells in Cryopyrin-Associated Periodic Syndromes

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations in the <i>NLRP3</i> gene leading to overproduction of IL-1β and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset capable of suppressing T-cell responses. As inflammasome products were previously found to induce MDSCs, we hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in CAPS. We studied neutrophilic MDSCs, their clinical relevance, and MDSC-inducing factors in a unique cohort of CAPS patients under anti-IL-1 therapy. Despite anti-IL-1 therapy and low clinical disease activity, CAPS patients showed significantly elevated MDSCs compared to healthy controls. MDSCs were functionally competent, as they suppressed polyclonal T-cell proliferation, as well as Th1 and Th17 responses. In addition, MDSCs decreased monocytic IL-1β secretion. Multiplex assays revealed a distinct pattern of MDSC-inducing cytokines, chemokines, and growth factors. Experimental analyses demonstrated that IL-1 cytokine family members and autoinflammation-associated alarmins differentially induced human MDSCs. Increased MDSCs might represent a novel autologous anti-inflammatory mechanism in autoinflammatory conditions and may serve as a future therapeutic target