Original ContributionInhaled glutathione decreases PGE2 and increases lymphocytes in cystic fibrosis lungs
Section snippets
Study design
The study population consisted of the previously reported 17 CF patients with mild to moderate lung disease (median FEV1 67% of predicted) (Table 1). Reduced GSH sodium salt (Biomedica Foscama, Ferentino, Italy) was reconstituted at concentrations of 200 or 300 mg/ml, resulting in a tonicity of 1301 or 1952 mosm/L. GSH was nebulized with a Pari LC Star nebulizer (Pari, Starnberg, Germany) and was inhaled three times daily. The total emitted volume was set to 1.5 ml by the AKITA inhalation
GSH administration
The aerosolized application of GSH for 2 weeks resulted in a three- to fourfold increase in BALF GSH levels with a mean pretreatment level of 2.9 μmol/L ± 0.7 SEM (substantially less than in normal individuals) and a mean posttreatment level of 12.4 μmol/L ± 4.2 SEM [22]. The GSH inhalation was well tolerated. Cough and an unpleasant odor from the GSH solution were reported by some patients.
Markers of oxidative stress
The delivery of substantial amounts of GSH into the lungs of CF patients did not change BALF
Discussion
We hypothesized that inhalation with GSH in CF patients would reduce oxidative stress, decrease inflammatory markers, and modulate lymphocyte response in BALF. The results show that the inhalation of GSH increased BALF lymphocytes, decreased BALF levels of PGE2, but did not affect the measured parameters of oxidative stress in BALF. No influence of GSH treatment on BALF levels of MPO, ascorbic acid, uric acid, and 8-isoprostane, as markers of oxidative stress, was found.
Furthermore, we found no
Acknowledgments
We thank Professor Luigi Inderst, Biomedica Foscama, Ferentino, Italy, and Omnia Pharma S.R.L., Italy, for providing the glutathione. This work was supported by grants from Mukoviszidose e.V., Bonn; CF-Selbsthilfe; Else-Kröner-Fresenius Stiftung; Friedrich-Baur-Stiftung; and a grant from the University and Science Program of the Ludwig-Maximilians-University (HWP).
References (69)
- et al.
Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches
Free Radic. Biol. Med.
(2000) Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation
Free Radic. Biol. Med.
(2001)- et al.
l-2-Oxothiazolidine-4-carboxylate, a cysteine precursor, stimulates growth and normalizes tissue glutathione concentrations in rats fed a sulfur amino acid-deficient diet
J. Nutr.
(1995) - et al.
The role of glutathione in lymphocyte-activation. 2. Effects of buthionine sulfoximine and 2-cyclohexene-1-one on early and late activation events
Int. J. Immunopharmacol.
(1991) - et al.
The lung as a privileged site for the beneficial actions of PGE(2)
Trends Immunol.
(2004) - et al.
Nuclear factor-kappa B mediates over-expression of cyclooxygenase–2 during activation of RAW 264.7 macrophages in selenium deficiency
Free Radic. Biol. Med.
(2002) - et al.
Assay-method for myeloperoxidase in human polymorphonuclear leukocytes
Anal. Biochem.
(1983) Towards the physiological-function of uric-acid
Free Radic. Biol. Med.
(1993)- et al.
Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles
Free Radic. Biol. Med.
(2005) - et al.
Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough
J. Allergy Clin. Immunol.
(2005)