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Inhaled glutathione decreases PGE2 and increases lymphocytes in cystic fibrosis lungs.
Free Radical Biol. Med. 39, 463-472 (2005)
Reduced glutathione (GSH), a major antioxidant and modulator of cell proliferation, is decreased in the bronchoalveolar lavage fluid (BALF) of cystic fibrosis (CF) patients. We previously have shown that GSH inhalation in CF patients significantly increased GSH levels in BALF and improved lung function (M. Griese et al., 2004, Am. J. Respir. Crit. Care Med. 169, 822-828). GSH depletion in vitro enhances susceptibility to oxidative stress, increases inflammatory cytokine release, and impairs T cell responses. We therefore hypothesized that an increase in GSH in BALF reduces oxidative stress, decreases inflammation, and modulates T cell responses in lungs of CF patients. BALF from 17 CF patients (median FEV1 67% (43-105%) of predicted) was assessed before and after GSH inhalation for total protein, markers of oxidative stress (8-isoprostane, myeloperoxidase, and ascorbic and uric acid), pattern of protein oxidation, prostaglandin E2 (PGE2), and proinflammatory cytokines. BALF cells were differentiated using cytospin slides, and lymphocytes were further analyzed by flow cytometry. Inhalation of GSH decreased BALF levels of PGE2 and increased CD4+ and CD8+ lymphocytes in BALF significantly but had no effect on markers of oxidative stress. BALF lymphocytes correlated positively with lung function, whereas levels of PGE2 showed an inverse correlation. The patients with the greatest improvement in lung function after GSH treatment also had the largest decline in PGE2 levels. We conclude that GSH inhalation in CF patients increases lymphocytes and suppresses PGE2 in the bronchoalveolar space. Thus, GSH primarily affected the pulmonary immune response rather than the oxidative status in CF patients. The effect of GSH inhalation on PGE2 levels and lymphocytes in CF warrants further investigation. © 2005 Elsevier Inc. All rights reserved.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
cystic fibrosis; oxidative stress; antioxidant; glutathione; GSH; PGE2; lymphocytes; bronchoalveolar lavage fluid; free radicals
ISSN (print) / ISBN
0891-5849
e-ISSN
1873-4596
Zeitschrift
Free Radical Biology and Medicine
Quellenangaben
Band: 39,
Heft: 4,
Seiten: 463-472
Verlag
Elsevier
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Lung Health and Immunity (LHI)
CCG Immune Regulation in Childhood (IMI-KIK)
CCG Immune Regulation in Childhood (IMI-KIK)