induction-of-mouse-lung-injury-by-endotracheal-injection-of-bleomycin

Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin

Pulmonary fibrosis is a hallmark of several human lung diseases with a different etiology. Since current therapies are rather limited, mouse models ...

Università Politecnica delle Marche

Systemic sclerosis or scleroderma (SSc) is a clinically heterogeneous disease of the connective tissue characterised by vascular, immune/inflammatory and fibrotic manifestations. Despite extensive investigations, the key pathogenic links between these disease hallmarks remain obscure, as well as the etiology underlying the beginning of this complex disorder. As for other diseases characterised by prominent autoimmune phenomena, the search for infectious agents responsible for immune tolerance breaks or molecular mimicry events has been a long-pursued issue. In this review, we summarise the current knowledge regarding the association of different viral infections with SSc, focusing mainly on those reports describing a mechanistic interplay between the viral agents and the pathogenesis of SSc. Moreover, we speculate on how viral infections may trigger additional pathogenic mechanisms recently proposed to contributing to SSc phenotype. 

Role of viral infections in the etiopathogenesis of systemic sclerosis.

Interstitial lung disease (ILD) affects about 90% of patients with systemic sclerosis (SSc). It is associated with a restrictive lung disease in only 30% of patients and is progressive in an even lower percentage. A low forced vital capacity at presentation, an extent of lung fibrosis >20% as detected by lung high-resolution computed tomography, high serum interleukin-6 levels, anti-topoisomerase I antibody positivity and diffuse cutaneous SSc are each associated with SSc-ILD progression. However, no such association is absolute. Treating patients with a recent deterioration of lung function may allow to capture those with active disease. To date, cyclophosphamide (CYC) is the only drug found to stabilize or improve lung function in randomized clinical trials, but its small beneficial effect is short lived. Therefore, immunosuppressive maintenance therapy after CYC treatment is warranted. At present, however, the best therapeutical strategy after CYC therapy both in responders and in non-responders to CYC is still controversial. Based on a review of the literature, we suggest an approach to the management of SSc-ILD.

Where are we going in the management of interstitial lung disease in patients with systemic sclerosis?

The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs. 

Article	Year
Role of viral infections in the etiopathogenesis of systemic sclerosis. Clinical and experimental rheumatology\| PubMed ID: 23910606	2013
Where are we going in the management of interstitial lung disease in patients with systemic sclerosis? Autoimmunity reviews\| PubMed ID: 25709096	2015
Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile. Current drug safety\| PubMed ID: 26463247	2016

Gianluca Moroncini

Biography

JoVE Journal Publications

Other Publications