Humanized monoclonal antibody against the chemokine CXCL-8 (IL-8) effectively prevents acute lung injury

Copyright 2009. Published by Elsevier B.V..

As one of the most important endogenous chemotactic factors for neutrophils, the chemokine CXCL8 (IL-8) is involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by massive neutrophil infiltration in the lung. Since neutralization of CXCL8 with polyclonal antibody has been shown to reduce the severity of ALI/ARDS in animal models, we explored the potential of humanized anti-CXCL8 antibody as a preventive or therapeutic agent for ALI. We used a 'two-hit' protocol to induce ALI in rabbits that showed extensive edema in the alveolar lumina, marked infiltration of neutrophils in the lung tissue, fibrin deposition in alveolar space, and destruction of pulmonary architecture, culminating in severe hypoxemia. Concomitant challenge with endotoxin after priming with oleic acid (OA) induced a marked elevation of CXCL8 level in bronchoalveolar lavage fluid. Treatment of the rabbits with a humanized anti-CXCL8 antibody prevented neutrophil infiltration in the lung in association with alleviated ALI syndrome. Our results indicate a promising future for utilization of humanized anti-CXCL8 antibody in the prevention and treatment of ALI and ARDS in human.

Medienart:

E-Artikel

Erscheinungsjahr:

2010

Erschienen:

2010

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

International immunopharmacology - 10(2010), 2 vom: 15. Feb., Seite 259-63

Sprache:

Englisch

Beteiligte Personen:

Bao, ZhiYao [VerfasserIn]
Ye, QingWei [VerfasserIn]
Gong, WangHua [VerfasserIn]
Xiang, Yi [VerfasserIn]
Wan, HuanYing [VerfasserIn]

Links:

Volltext

Themen:

2UMI9U37CP
9001-31-4
Antibodies, Monoclonal
Endotoxins
Fibrin
Interleukin-1
Interleukin-8
Journal Article
Oleic Acid
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 20.04.2010

Date Revised 09.12.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2009.11.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM192795988