Idiopathic pulmonary fibrosis: Current and future treatment.

OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development. DATA SOURCE: The data were obtained from the Randomized Controlled Trials and scientific studies published in English literature. We used search terms related to IPF, antifibrotic treatment, lung transplant, and management. RESULTS: Etiopathogenesis of IPF is not fully understood, and treatment options are limited. Pathological features of IPF include extracellular matrix remodeling, fibroblast activation and proliferation, immune dysregulation, cell senescence, and presence of aberrant basaloid cells. The mainstay therapies are the oral antifibrotic drugs pirfenidone and nintedanib, which can improve quality of life, attenuate symptoms, and slow disease progression. Unilateral or bilateral lung transplantation is the only treatment for IPF shown to increase life expectancy. CONCLUSION: Clearly, there is an unmet need for accelerated research into IPF mechanisms so that progress can be made in therapeutics toward the goals of increasing life expectancy, alleviating symptoms, and improving well-being.

Effect of oxytocin on lipid accumulation under inflammatory conditions in human macrophages.

INTRODUCTION AND AIMS: Oxytocin (OT) is a neuropeptide hormone secreted by the posterior pituitary gland. Deficits in OT action have been observed in patients with behavioral and mood disorders, some of which correlate with an increased risk of cardiovascular disease (CVD). Recent research has revealed a wider systemic role that OT plays in inflammatory modulation and development of atherosclerotic plaques. This study investigated the role that OT plays in cholesterol transport and foam cell formation in LPS-stimulated THP-1 human macrophages. METHODS: THP-1 differentiated macrophages were treated with media, LPS (100 ng/ml), LPS + OT (10 pM), or LPS + OT (100 pM). Changes in gene expression and protein levels of cholesterol transporters were analyzed by real time quantitative PCR (RT-qPCR) and Western blot, while oxLDL uptake and cholesterol efflux capacity were evaluated with fluorometric assays. RESULTS: RT-qPCR analysis revealed a significant increase in ABCG1 gene expression upon OT + LPS treatment, compared to LPS alone (p = 0.0081), with Western blotting supporting the increase in expression of the ABCG1 protein. Analysis of oxLDL uptake showed a significantly lower fluorescent value in LPS + OT (100pM) -treated cells when compared to LPS alone (p < 0.0001). While not statistically significant (p = 0.06), cholesterol efflux capacity increased with LPS + OT treatment. CONCLUSION: We demonstrate here that OT can attenuate LPS-mediated lipid accumulation in THP-1 macrophages. These findings support the hypothesis that OT could be used to reduce pro-inflammatory and potentially atherogenic changes observed in patients with heightened CVD risk. This study suggests further exploration of OT effects on monocyte and macrophage cholesterol handling in vivo.

Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets.

Oxytocin: Potential to mitigate cardiovascular risk.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, despite multiple treatment options. In addition to elevated lipid levels, oxidative stress and inflammation are key factors driving atherogenesis and CVD. New strategies are required to mitigate risk and most urgently for statin-intolerant patients. The neuropeptide hormone oxytocin, synthesized in the brain hypothalamus, is worthy of consideration as a CVD ancillary treatment because it moderates factors directly linked to atherosclerotic CVD such as inflammation, weight gain, food intake and insulin resistance. Though initially studied for its contribution to parturition and lactation, oxytocin participates in social attachment and bonding, associative learning, memory and stress responses. Oxytocin has shown promise in animal models of atherosclerosis and in some human studies as well. A number of properties of oxytocin make it a candidate CVD treatment. Oxytocin not only lowers fat mass and cytokine levels, but also improves glucose tolerance, lowers blood pressure and relieves anxiety. Further, it has an important role in communication in the gut-brain axis that makes it a promising treatment for obesity and type 2 diabetes. Oxytocin acts through its receptor which is a class I G-protein-coupled receptor present in cells of the vascular system including the heart and arteries. While oxytocin is not used for heart disease at present, residual CVD risk remains in a substantial portion of patients despite multidrug regimens, leaving open the possibility of using the endogenous nonapeptide as an adjunct therapy. This review discusses the possible role for oxytocin in human CVD prevention and treatment.