Critical Care |

Erythropoietin (EPO) Inhibits the Expression of Tumor Necrosis Factor-Alpha (TNF-α) in Bleomycin (BLM)-Induced Pulmonary Fibrosis in Rats FREE TO VIEW

Drosos Tsavlis, MD; Anastasia Tektonidou, NHA; Afroditi Papadopoulou, MD; Anna Tzoumaka, MD
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Aristotle University of Thessaloniki, Thessaloniki, Greece

Chest. 2014;146(4_MeetingAbstracts):245A. doi:10.1378/chest.1990396
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SESSION TITLE: Critical Care Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: The tumor necrosis factor-alpha (TNF-a) is produced by alveolar macrophages in response to bleomycin (BLM) exposure. This cytokine has been linked to BLM-induced pulmonary inflammation and apoptosis, both early drug effects, and to lung fibrosis, the ultimate toxic effect of BLM. Erythropoietin, on the other hand, is a multiple functional cytokine with anti-inflammatory, anti-oxidative and anti-apoptotic properties. Aim of the present study was to investigate the role of EPO on the expression of TNF-a in BLM-induced pulmonary fibrosis in rats.

METHODS: Fifty Wistar rats (300gr) were divided into five groups of 10 animals each: 1) control animals, 2) intratracheal and intraperitoneal injection of saline (0.5ml/kg), 3) BLM hydrochloride (7.5mg/kg) intratracheal injection, 4) BLM hydrochloride (7.5mg/kg) intratracheal injection followed by EPO intraperitoneal injection (2000 iu/kg), 5) saline (0.5ml/kg) intratracheal injection followed by EPO intraperitoneal injection (2000 iu/kg). All rats were sacrified after 14 days. The expression of TNF-a was immunohistochemically measured and a scale of four grades (A:0-25%, B:25-50%, C:50-75%, D:75-100%) was used to evaluate it.

RESULTS: In groups 1,2 and 5 (control groups), TNF-a was expressed only in the two lower grades of the scale (A:80% and B:20%). In group 3, TNF-a was expressed in the high grades (C:10% and D:90%). Finally, in group 4, the cytokine in question was expressed only in the low grades (A:70% and B:30%), almost like the control groups.The expression of TNF-a took place in the high grades for group 3 (BLM group) and in the lower grades for group 4 (BLM+EPO group) (p<0.001 and p<0.05 respectively).

CONCLUSIONS: Treatment with EPO significantly ameliorated the extent and severity of the BLM-induced toxicity in lung tissue. The cytokine TNF-a had a significantly lower expression in the group of animals (group 4) which were administrated with EPO, compared with the group of BLM (group 3).

CLINICAL IMPLICATIONS: These findings suggest tha further investigation must be done in order to clarify the underlying mechanisms of the attenuating effect of EPO on the expression of TNF-a in pulmonary fibrosis. Erythropoietin may be used as a potential target for pulmonary fibrosis' treatment in the future.

DISCLOSURE: The following authors have nothing to disclose: Drosos Tsavlis, Anastasia Tektonidou, Afroditi Papadopoulou, Anna Tzoumaka

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