Review: New perspectives in the treatment of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most frequent idiopathic interstitial pneumonia with a prevalence ranging from 5 to 15 per 100,000 persons, and above 175 per 100,000 in the older population. IPF is a relentlessly progressive fibrotic lung disorder leading to death within a median duration of 3 years. It was hypothesized in the 1970s that pulmonary fibrosis initiates as an "alveolitis" progressing to interstitial fibrosis with connective tissue deposition, derangement of the lung architecture and functional impairment. However, in vitro studies indicated that alveolar/bronchiolar injured epithelial cells can drive the fibrotic process in the absence of macrophages and with minimal inflammation. This, together with the inability of classic immunosuppressive therapy to cure IPF, generated new pathogenesis paradigms and intense research into the role of the lack or the excessive production of anti-fibrotic or profibrotic mediators, oxidant injury, exaggerated coagulation, thus leading to investigate new treatment strategies. Preliminary results of some of such trials have shown significant reductions in lung function decline, disease exacerbation and mortality.

Bleomycin induces upregulation of lysyl oxidase in cultured human fetal lung fibroblasts

“…Here, we showed that BLM significantly enhanced LO catalytic activity in concomitant with elevation of Cu levels in the HLF-conditioned media. Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), has been thought as a result of an initial injury to the lung that causes the recruitment of inflammatory cells, release of cytokines and eventual increase of fibroblast activity leading to parenchymal remodeling [19,20] . Although many progresses have been made in explanation of pathogenesis of IPF in recent years, the precise mechanism of IPF remains unclear and thus there is no effective treatment for IPF.…”

T regulatory cells and attenuated bleomycin-induced fibrosis in lungs of CCR7-/- mice

“…Idiopathic pulmonary fibrosis (IPF) is an irreversible, fatal lung disease, marked by progressive deterioration of lung function due to an uncontrolled repair process [1]. The pathogenesis of IPF is not completely understood, which is reflected in the lack of successful treatments and good diagnostic markers.…”

Review article: anti‐fibrotic agents for the treatment of Crohn’s disease – lessons learnt from other diseases

“…Azathioprine, the most common immunosuppressive agent used for the treatment of patients with CD, along with other immunosuppressant agents, such as cyclophosphamide and methotrexate, has been used for the treatment of several chronic inflammatory diseases. This drug was effective for the treatment of mild cases of retroperitoneal fibrosis or in severe disease for maintenance therapy after intravenous cyclophosphamide treatment 14 and may have some additional effects when administered with corticosteroids in fibrotic pulmonary disease 10,15–17 . The successful use of azathioprine in preventing post‐operative recurrence of CD, even in the absence of studies designed to evaluate its effect on intestinal fibrosis, supports the hypothesis that thiopurines can prevent or at least slow the fibrotic process in patients with CD 18 …”

“…The anti‐fibrotic effect of corticosteroids is a very well‐known phenomenon, causing deficiency in general wound healing. This effect results from a decrease in collagen synthesis 3 and for this reason, positive effects have been observed with corticosteroids in other fibrotic diseases, such as retroperitoneal fibrosis, 6,7 systemic sclerosis 8 and idiopathic pulmonary fibrosis 9,10 . However, there are several drawbacks associated with steroid use: first of all, long‐term systemic use of steroids is not recommended because of several significant side effects and secondly, there is some doubt as to whether this anti‐fibrotic action occurs in intestinal smooth muscle cells.…”

“…These may be the differentiation of stem cells, perycites, fibrocytes or stellate cells that are activated by cytokines, chemokines and growth factors (Figure 1). 6 The possible inhibitory mechanisms have been examined in several pathologies affecting different organs, such as systemic sclerosis, liver cirrhosis, nephrosclerosis in diabetic and IgA nephropathy, rheumatoid arthritis, and chronic pancreatitis 7–10 . In spite of all the progress that has been made in advancing our understanding of the pathophysiology of these conditions, clinical treatment remains a major challenge.…”