@article{3084037,
    title = "Suboptimal erythropoietic response to hypoxemia in idiopathic pulmonary
fibrosis",
    author = "Tsantes, A and Tassiopoulos, S and Papadhimitriou, SI and Bonovas, S and and Kavalierou, L and Vaiopoulos, G and Meletis, I",
    journal = "Chest",
    year = "2003",
    volume = "124",
    number = "2",
    pages = "548-553",
    publisher = "Elsevier",
    issn = "0012-3692, 1931-3543",
    doi = "10.1378/chest.124.2.548",
    keywords = "chronic inflammation; cytokines; idiopathic pulmonary fibrosis;
ineffective erythropoiesis",
    abstract = "Background and study objectives: 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.
Subjects: 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.
Methods: 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.
Results: 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).
Conclusions: 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."
}