G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia

Hierholzer, Christian; Kelly, Edward; Lyons, V.; Roedling, Eva; Davies, Paul; Billiar, Timothy R.; Tweardy, David J.

doi:10.1002/jlb.63.2.169

Cited by 59 publications

(43 citation statements)

References 22 publications

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“…The hypothesis that lung injury could result from locally increased levels of G-CSF and subsequent neutrophil recruitment and activation was later confirmed by intratracheal injection of G-CSF; BAL fluid and lung biopsies revealed marked edema of the interstitium and alveoli. 5 Iijima et al 6 found significant increases in the rheological activity of leukocytes and serum levels of granulocyte elastase in patients receiving G-CSF as compared to those in untreated subjects. Our patient developed an acute, systemic inflammatory reaction which started during leukapheresis and culminated in serosal inflammation and effusion, hypoxemia, shock, edema, neurologic changes and hepatic injury.…”

Section: Discussionmentioning

confidence: 98%

Life-threatening capillary leak syndrome after G-CSF mobilization and collection of peripheral blood progenitor cells for allogeneic transplantation

Azevedo

Tabak

2001

Bone Marrow Transplant

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Summary:We report a case of capillary leak syndrome in a 37-year-old female PBPC donor who received G-CSF 900 g/day for 4 days and underwent leukapheresis. This lady had remained well and stable despite marked leukocytosis during G-CSF treatment, but developed hypotension during leukapheresis, quickly followed by hypoxemia, ascites, pericardial and pleural effusion, shock, edema, neurologic changes and hepatocellular injury. Upon G-CSF withdrawal, dopamine and crystalloid infusion, methylprednisolone treatment and suspension of apheresis, the clinical situation fully reversed. We hypothesize that leukapheresis, in the presence of marked leukocytosis and high doses of G-CSF, may have triggered neutrophil activation and the release of inflammatory mediators, resulting in tissue damage and systemic manifestations of increased capillary permeability. Bone Marrow Transplantation (2001) 28, 311-312. Keywords: G-CSF; capillary leak syndrome; leukapheresis; peripheral blood progenitor cell transplantation A 37-year-old white female agreed to donate allogeneic G-CSF-mobilized PBPC for her brother. She was asymptomatic, in good health, and used no medications. Her past medical history was unremarkable. Physical examination was normal except for moderate obesity and bradycardia. She had a normal chest film and echocardiogram. ECG showed sinus bradycardia. Serum biochemistry and coagulation tests were normal, Hb was 12.9 g/dl, hematocrit 38%, WBC 6.4 × 10 9 /l (ANC 3.1 × 10 9 /l) and platelets 322 × 10 9 /l. She received G-CSF 900 g s.c. daily in two divided doses for 4 days (10 g/kg/day). On the fifth day, the WBC count was 90.5 × 10 9 /l. Her only symptom thus far had been moderate headache which subsided with acetaminophen. A last dose of G-CSF was given. Three hours after the start of apheresis, she was pale and hypotensive, complaining of respiratory discomfort, nausea and weakness. Intravenous saline and calcium gluconate were given, with partial improvement. Apheresis was stopped after 5 h and she received another dose of G-CSF, because the number of CD34 + cells collected had been insufficient. Returning in the next morning, she complained of dyspnea, pleuritic pain and 'tightness in the chest'. Hematocrit was 33% and WBC 74.7 × 10 9 /l. Minutes later, she fainted and was admitted to the emergency room with severe hypotension, pallor, pulmonary rales, hypoxemia, cyanosis and confusion. A CT scan showed ascites, pericardial fluid and bilateral pleural effusion (Figures 1 and 2). Pericardiocentesis yielded clear fluid with 65 cells/mm 3 (77% neutrophils), 4.2 g/dl protein and LDH 512 U/l. Pleural fluid had the same characteristics. Her hemodynamic status improved with i.v. saline and dopamine. She remained confused and agitated for the next 12 h, normalizing her mental status gradually thereafter. A CT scan of the head was normal. Her weight was 8 kg above baseline. Her previously normal alanine aminotransferase peaked at 568 U/l (normal: Ͻ37 U/l). Bilirubin and alkaline phosphatase were unchanged. Hypoalbuminemia (3....

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Section: Discussionmentioning

confidence: 98%

Life-threatening capillary leak syndrome after G-CSF mobilization and collection of peripheral blood progenitor cells for allogeneic transplantation

Azevedo

Tabak

2001

Bone Marrow Transplant

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“…In addition, experimental models show that intravenous instillation of recombinant G-CSF can exacerbate pre-existing acute lung injury [31±33]. Furthermore, it has recently been reported that G-CSF alone can induce acute lung injury when introduced directly into the lungs of rats [34]. Doses of 300±3,000 ng recombinant human G-CSF introduced intratracheally caused hypoxia, marked pulmonary oedema and pulmonary neutrophilia.…”

Section: Discussionmentioning

confidence: 99%

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

Aggarwal¹,

Cs²,

Evans³

et al. 2000

Eur Respir J

177

124

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Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)‐8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM‐CSF and G‐CSF in the lungs of patients with ARDS and determine their relationship relative to IL‐8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme‐linked immunosorbent assay. GM‐CSF, G‐CSF and IL‐8 were all increased in the patients compared to healthy controls but concentrations of GM‐CSF were much lower than those of G‐CSF and IL‐8 (GM‐CSF

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“…Hierholzer et al have shown that installing G-CSF into the lungs of rats by intratracheal injection resulted in recruitment of neutrophils, lung injury, and impaired pulmonary function [44].…”

Section: Biotherapeutic Agentsmentioning

confidence: 99%

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

Briasoulis

Pavlidis

2001

The Oncologist

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Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The Oncologist 2001;6:153-161 www.TheOncologist.com Correspondence: Evangelos Briasoulis, M.D., Medical Oncology Department, Ioannina University, Ioannina, 45110, Greece. Telephone and Fax: 30-651-99394; e-mail: ebriasou@otenet.gr. Received August 15, 2000; accepted for publication November 30, 2000. ©AlphaMed Press 1083-7159/2001 INTRODUCTIONSeveral cancer therapeutic drugs are known to induce pulmonary damage, which may result in a variety of clinicopathologic syndromes with minor to severe clinical consequences [1]. Clinical syndromes associated with drug-induced pulmonary toxicity include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema (NCPE)/acute respiratory distress syndrome (ARDS). These syndromes share a similar symptomatology but differ in regard to the time-relation to cancer treatment, the radiographic findings, the duration of pulmonary damage, and the long-term outcome [2]. Non-specific symptomatology of cough, progressive dyspnea, and often a low-grade fever alert clinicians confronted with the diagnostic challenge to recognize subclinical syndromes and differentiate fully developed drug-induced pulmonary reactions from lung injuries caused by infectious, cardiac, and neoplastic causes.

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G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia

Cited by 59 publications

References 22 publications

Life-threatening capillary leak syndrome after G-CSF mobilization and collection of peripheral blood progenitor cells for allogeneic transplantation

Life-threatening capillary leak syndrome after G-CSF mobilization and collection of peripheral blood progenitor cells for allogeneic transplantation

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

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