Infliximab Treatment in a Patient with Systemic Sclerosis Associated with Lung Fibrosis and Pulmonary Hypertension

Bargagli, Elena; Galeazzi, Mauro; Bellisai, Francesca; Volterrani, Luca; Rottoli, Paola

doi:10.1159/000090248

Cited by 43 publications

(29 citation statements)

References 40 publications

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“…131 The TNFα antibody infliximab reduced pulmonary pressures and improved the quality of life in a patient with severe PAH secondary to advanced scleroderma. 164 These data suggest that the metabolic and inflammatory theories in PAH overlap and may even potentiate each other.…”

Section: Metabolic Changes In Activated Inflammatory Cellsmentioning

confidence: 93%

The Metabolic Theory of Pulmonary Arterial Hypertension

Paulin

Michelakis

2014

Circulation Research

264

243

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A lthough traditionally pulmonary arterial hypertension (PAH) has been described as a disease exclusively of the pulmonary arteries, there is now evidence that PAH involves many other organs (Figure 1). For example, the hearts (right ventricle [RV]) of patients with PAH decompensate and fail at a much faster rate compared with what one would expect extrapolating from the left ventricle, suggesting that there may be mechanisms intrinsic to the RV that promote RV failure in PAH. Even patients with idiopathic PAH, without coexistent autoimmune disorders, have circulating immune cells that are activated, producing a strong inflammatory environment and potentially contributing to the malaise and weakness that patients with PAH have. Recent evidence suggests that, perhaps, their skeletal muscles (the target organs in the metabolic syndrome) have abnormalities similar to patients with diabetes mellitus, obesity, and

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Section: Metabolic Changes In Activated Inflammatory Cellsmentioning

confidence: 93%

The Metabolic Theory of Pulmonary Arterial Hypertension

Paulin

Michelakis

2014

Circulation Research

264

243

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“…In clinical studies, it has been shown that IFX diminishes pulmonary fibrosis via blocking TNF-α [41,42], and pulmonary fibrosis is not a contraindication for TNF-α inhibitor therapy of rheumatology [43]. Altintas et al [27] have evaluated the preventive effect of IFX in bleomycininduced pulmonary fibrosis, eliminating the harmful effect of IFX per se on pulmonary fibrosis.…”

Section: Western Blot Analysis Of Nf-κb P65 and I-κb Protein Expressionmentioning

confidence: 99%

Subcutaneous administration of infliximab-attenuated silica-induced lung fibrosis

Zhang

Sui

Gao

et al. 2017

Int J Occup Med Environ Health

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Objectives: To investigate the influence of the anti-tumor necrosis factor-α infliximab (IFX) in the case of rats with silicosis. Material and Methods: Forty-eight Wistar rats were randomly divided into 3 groups. The study group (N = 16) -silicosis was induced by intratracheal instillation of 50 mg silica on day 1, and IFX was subcutaneously administered at a dose of 15 mg/kg of body weight from day 2 to day 6, the vehicle group (N = 16) -silica used as the study group but without IFX, the sham group (N = 16) -1 ml of saline was intratracheal-used. Eight rats in each group were euthanized on day 7 and on day 14, respectively. Lung tissue sections were stained with hematoxylin and eosin or Masson's trichromedye. The nuclear factor-κB p65 (NF-κB p65) positioning in the lung tissues were determined by immunohistochemical staining. Levels of tumor necrosis factor α (TNF-α) in rat serum and bronchoalveolar lavage fluid were measured with enzyme linked immunosorbent assay. The inducible nitric oxide synthase (iNOS) mRNA in the lung tissues was measured by quantitative real-time polymerase chain reaction, as well as inhibitor protein-κB (I-κB) and NF-κB p65 expression were measured quantitatively by western blotting. Results: Silica installation increased the lung tissues inflammation reaction, oxidative stress and pulmonary fibrosis. Infliximab treatment significantly improved silica-induced lung pathological changes (inflammatory cells, collagen deposition), decreased the TNF-α inhibited NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS). Conclusions: Infliximab may improve silica-induced pulmonary inflammation by decreasing the TNF-α, inhibiting NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS), which suggest that IFX has potential role in the treatment of silica-induced lung damage. Int J Occup Med Environ Health 2018;31(4):503 -515

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“…45 An open-label pilot study in 16 systemic sclerosis patients demonstrated improvement in skin scores with reduction in collagen secretion noted from cultured lesional fibroblasts (Table 1). [46][47][48] In contrast, there is evidence to suggest that TNFa is a potentially anti-fibrogenic cytokine and its blockade might consequently promote fibrosis. In some studies, TNFa can exhibit anti-fibrotic properties by reducing the expression of collagen and CTGF in dermal fibroblasts, 49 and via suppression of TGFb signaling through nuclear factor (NF)-kappa (K) B induction of Smad 7 in other cell types.…”

Section: Tumor Necrosis Factor Alpha (Tnf)mentioning

confidence: 99%

Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD

Jacob

Targan

Shih

2016

United European Gastroenterology Journal

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The frequency of fibrosing Crohn's disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis.

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Infliximab Treatment in a Patient with Systemic Sclerosis Associated with Lung Fibrosis and Pulmonary Hypertension

Cited by 43 publications

References 40 publications

The Metabolic Theory of Pulmonary Arterial Hypertension

The Metabolic Theory of Pulmonary Arterial Hypertension

Subcutaneous administration of infliximab-attenuated silica-induced lung fibrosis

Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD

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