Recombinant Cytokine Treatment for Scleroderma

Varga, John

doi:10.1001/archderm.1997.03890410093013

Cited by 22 publications

(3 citation statements)

References 39 publications

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“…However, IFN-γ may have an indirect profibrotic effect by stimulating TGF-β and ET1 synthesis in microvascular ECs, inducing EndoMT, and promoting vascular injury (133). Therapeutic trials of IFN-γ for SSc patients have demonstrated modest and inconsistent improvement in skin fibrosis, but a randomized trial in idiopathic pulmonary fibrosis showed no benefit, and enthusiasm for this form of therapy has waned in recent years (134, 135).…”

Section: Excessive Fibrosismentioning

confidence: 99%

Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities

Varga

Trojanowska

Kuwana

2017

Journal of Scleroderma and Related Disorders

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274

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that results in irreversible scarring and organ failure. In other word, fibrosis is the end-result of a cascade of vascular and immune responses to environmental injury, and represents a failed tissue repair process. There have been advances in understanding of pathogenic processes that reflect the interplay between immune-inflammatory processes and vasculopathy and fibrosis. This review focuses on recent insights of functional consequences of SSc, highlighting three major characteristics of SSc; microvasculopathy, excessive fibrosis, and immune dysregulation. Microvasculopathy Although, widespread structural changes of the microvasculature are well documented in SSc patients, many aspects of SSc vasculopathy, including the nature of the injury and the fate of injured endothelial cells (ECs), remain poorly understood. Nevertheless, studies in recent years have brought a wealth of new information on the molecular and cellular mechanisms contributing to SSc vasculopathy. Diverse triggers have been implicated in inducing EC damage, including infection, immune-mediated cytotoxicity, anti-endothelial autoantibodies (AECAs), and ischemia-reperfusion injury. The resulting pathogenic changes in ECs may also vary and may include EC apoptosis, endothelial to mesenchymal transition (EndoMT), and other forms of EC activation. A bi-directional

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Section: Excessive Fibrosismentioning

confidence: 99%

Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities

Varga

Trojanowska

Kuwana

2017

Journal of Scleroderma and Related Disorders

Self Cite

274

251

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show abstract

“…Although preliminary data [19] suggested some, however, nonsignificant benefit of IFN-c treatment in patients with pulmonary fibrosis, other studies failed to show any effects of IFN-c in patients with systemic sclerosis [20][21][22]. Overall, there was only a moderate (nonsignificant) effect on skin sclerosis and no significant change in pulmonary function [23]. However, these studies were limited by the fact that histopathological analysis of pulmonary fibrosis was lacking [19][20][21][22] and the dosage of IFN-c treatment was lower.…”

Section: Discussionmentioning

confidence: 99%

“…However, these studies were limited by the fact that histopathological analysis of pulmonary fibrosis was lacking [19][20][21][22] and the dosage of IFN-c treatment was lower. All studies reported side-effects of IFN-c treatment in up to 65% of the study population and the mean drop-out rate resulting from sideeffects was 28% [23].…”

Section: Discussionmentioning

confidence: 99%