losartan-potassium and Pulmonary-Fibrosis

Despite the severe derangement of gas exchange in the advanced stages of idiopathic pulmonary fibrosis (IPF), secondary erythrocytosis is either absent or much lower than is seen in chronic obstructive pulmonary disease (COPD) with comparable hypoxemia. This study investigates the differences in erythropoiesis between IPF and COPD, searching for the possible underlying mechanisms.. The study included 32 patients with COPD, 18 patients with IPF, all with overt hypoxemia (PO(2) <65 mmHg), and 34 healthy controls. Erythrocytic parameters and serum erythropoietin (EPO) levels were assessed for all subjects. In a number of patients from both groups, the development of erythroid colonies grown from peripheral blood mononuclear cells was assayed in semisolid methylcellulose cultures and compared to cultures of control cells, in the presence of patient or control serum.. Hb and serum EPO levels were significantly higher in the COPD group than in IPF patients and controls. However, the number of BFU-E colonies obtained from mononuclear cells of IPF patients was clearly higher than in COPD patients when the same culture medium was used. Unlike COPD sera, IPF sera induced a significant growth inhibition of erythroid bursts arising from mononuclear cells of both patients and controls.. Our findings suggest a kind of ineffective erythropoiesis in IPF. Defective EPO production and inhibitory effect on erythropoiesis exerted by pro-inflammatory cytokines released from alveolar macrophages may be implicated in the suboptimal erythropoietic response. However, the possible involvement of other factors affecting erythropoiesis in IPF requires further investigation.

Topics: Aged; Blood Gas Analysis; Erythrocyte Count; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Hypoxia; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis

Organ toxicity induced by chemotherapeutic drugs is a serious obstacle in the effective treatment of patients suffering from cancer and autoimmune disease. A strong association exists between pulmonary toxicity, particularly fibrosis, and chemotherapeutic drugs. Attempts have been made to identify compounds capable of suppressing fibrosis. In addition to its erythropoietic activity, erythropoietin (EPO) has been shown to have effects on nonhemopoietic cells. Therefore, we postulated that EPO may exert beneficial effects on lung tissue during chemotherapy. To test our hypothesis, we investigated pulmonary changes caused by bleomycin, a fibrosis-inducing agent, in animals treated with the drug alone and in combination with EPO. Fibrosis, cellular alterations and structural changes were assayed by blind analysis of the lung sections. A 6-fold decrease in the number of prominent endothelial cells--suspected to be indicative of cellular activation and inflammatory response--was observed in lung sections derived from mice treated with bleomycin and EPO compared to animals injected with bleomycin alone (p < 0.008). Additionally, there was twice the number of ICAM1-positive endothelial cells in animals treated with bleomycin alone compared with the number in the bleomycin and EPO-treated group (p < 0.05). Alveolar mononuclear phagocytic hyperplasia was reduced by as much as 100% in animals treated with bleomycin and EPO compared to animals treated with bleomycin alone (p < 0.03). Finally, a 5-fold decrease in interstitial fibrosis was observed in lung sections obtained from animals treated with bleomycin and EPO (p < 0.02). We conclude that EPO can ameliorate drug-induced fibrosis and endothelial damage caused by chemotherapeutic agents.

Topics: Animals; Antineoplastic Agents; Bleomycin; Disease Models, Animal; Erythropoietin; Female; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory process characterized by severe derangement of gas exchange in the advanced stages of disease. However, erythrocytosis is infrequent in IPF. The aim of this study was to investigate the potential relation between the blunted erythropoietic response and the chronic inflammation.. Nine patients (6 men and 3 women) with IPF and profound hypoxemia (PO(2) < 65 mm Hg) and 34 sex- and age-matched healthy volunteers participated in the study.. We evaluated the hematologic parameters, serum erythropoietin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 levels. We also studied the development of burst-forming unit-erythroid (BFU-E)-derived colonies in semisolid methylcellulose cultures in blood samples from all patients.. Hemoglobin and serum erythropoietin levels were almost comparable between the two studied groups. On the contrary, serum TNF-alpha, IL-6, and IL-8 values were significantly higher in patients with IPF (p < 0.05, p < 0.01, and p < 0.001, respectively). IPF sera induced a significant growth inhibition of erythroid bursts arising from mononuclear cells of either patients or control subjects compared with heat-inactivated AB serum (p < 0.05 and p < 0.01, respectively). Moreover, there was an apparent increment in the number of BFU-E colonies when patients' mononuclear cells were cultured in comparison with those of healthy subjects (p < 0.05).. Our findings suggest that in IPF there is an increased number of primitive erythroid progenitors, which fail to proliferate and differentiate in vivo, suggesting a kind of ineffective erythropoiesis. As a consequence, hemoglobin levels do not rise in proportion to the severity of hypoxemia. Cytokines released from alveolar macrophages seem to have not only local but also systemic effects, since the serum of these patients directly suppressed erythropoiesis; however, the suboptimal erythropoietic response to hypoxia cannot be entirely attributed to this suppression. It is possible that several other factors interfere, synergistically or additively.

Topics: Aged; Case-Control Studies; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pulmonary Fibrosis; Tumor Necrosis Factor-alpha

The aim of this study was to assess the erythropoietic response to hypoxaemia in patients with diffuse idiopathic pulmonary fibrosis (DIPF), and to speculate on the underlying mechanisms. Patients on an established chronic respiratory failure due to DIPF or chronic obstructive pulmonary disease (COPD) were studied. The erythropoietic response to hypoxaemia in both conditions was assessed. We studied 18 patients with DIPF and 29 patients with COPD in respiratory failure in a stable stage, free from acute infection and congestive heart failure. Blood gases, erythrocytic parameters, as well the serum levels of iron, ferritin and erythropoietin were determined. All the DIPF patients studied, apart from two, had normal or subnormal haematocrit values. The patients with COPD had an inconsistant response to hypoxaemia; 12 had normal or subnormal haematocrit values and the remaining 17 were erythraemic. The mean value of erythropoietin (EPO) in both DIPF and COPD patients was significantly higher than normal. In conclusion, patients with DIPF exhibit a lack of erythropoietic response to hypoxaemia, despite the augmented erythropoietin levels. This may reflect a defective bone marrow erythropoietic response in DIPF patients. It is suggested that the pathophysiology of DIPF underlies this mechanism.

Topics: Adult; Aged; Aged, 80 and over; Blood Gas Analysis; Erythropoiesis; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Hypoxia; Iron; Lung Diseases, Obstructive; Male; Middle Aged; Pulmonary Fibrosis; Reference Values; Regression Analysis

Topics: Aged; Arteries; Blood Gas Analysis; Erythrocytes; Erythropoietin; Heart Failure; Hematocrit; Humans; Hypoxia; Leukocyte Count; Lung Diseases; Middle Aged; Pulmonary Embolism; Pulmonary Fibrosis; Respiratory Insufficiency; Reticulocytes