Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.
BACKGROUND
Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence.


METHODS
Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration.


RESULTS
Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed.


CONCLUSIONS
It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals.
Holroyd
K J
KJ
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Buhl
R
R
Borok
Z
Z
Roum
J H
JH
Bokser
A D
AD
Grimes
G J
GJ
Czerski
D
D
Cantin
A M
AM
Crystal
R G
RG
D000328:Adult; D000336:Aerosols; D002455:Cell Division / Q000187:drug effects; D004848:Epithelium / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000008:administration & dosage* / Q000172:deficiency* / Q000494:pharmacology; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000737:chemistry*; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects
D000336:Aerosols; D005978:Glutathione